Primary Hepatocytes: Current Understanding of the Regulation of Metabolic Enzymes and Transporter Proteins, and Pharmaceutical Practice for the Use of Hepatocytes in Metabolism, Enzyme Induction, Transporter, Clearance, and Hepatotoxicity Studies

REFERENCES

• (CDER/FDA) Center For Drug Evaluation and Research/FDA. Guidance for Industry. Drug Metabolism/Drug Interaction Studies in the Drug Development Process: Studies in Vitro. Center for Drug Evaluation and Research, Food and Drug Adminsitration, Rockville, MD 1997
   Google Scholar
• Allen S. W., Mueller L., Williams S. N., Quattrochi L. C., Raucy J. The use of a high-volume screening procedure to assess the effects of tiutqry vlqvonoits0o∼ xuman cyp1a1 expression. Drug Metab. Dispos. 2001; 29(8)1074–1079
   PubMed Web of Science ®Google Scholar
• Andersson T. Pharmacokinetics, metabolism and interactions of acid pump inhibitors. Focus on omeprazole, lansoprazole and pantoprazole. Clin. Pharmacokinet. 1996; 31(1)9–28
   PubMed Web of Science ®Google Scholar
• Andersson T. B., Sjoberg H., Hoffmann K. J., Boobis A. R., Watts P., Edwards R. J., Lake B. G., Price R. J., Renwick A. B., Gomez-Lechon M. J., Castell J. V., Ingelman-Sundberg M., Hidestrand M., Goldfarb P. S., Lewis D. F., Corcos L., Guillouzo A., Taavitsainen P., Pelkonen O. An assessment of human liver-derived in vitro systems to predict the in vivo metabolism and clearance of almokalant. Drug Metab. Dispos. 2001; 29(5)712–720
   PubMed Web of Science ®Google Scholar
• Aninat C., Piton A., Glaise D., Le Charpentier T., Langouët S., Morel F., Guguen-Guillouzo C., Guillouzo A. Expression of cytochromes p450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells. Drug Metab. Dispos. 2006; 34: 75–83
   PubMed Web of Science ®Google Scholar
• Annaert P. P., Brouwer K. L. Assessment of drug interactions in hepatobiliary transport using rhodamine 123 in sandwich-cultured rat hepatocytes. Drug Metab. Dispos. 2005; 33(3)388–394
   PubMed Web of Science ®Google Scholar
• Arand M., Herrero, Plana M. E., Hengstler J. G., Lohmann M., Cronin A., Oesch F. Detoxification strategy of epoxide hydrolase the basis for a threshold in chemical carcinogenesis. EXCLI J. 2003; 22: 22–30
   Google Scholar
• Arlotto M. P., Trant J. M., Estabrook R. W. Measurement of steroid hydroxylation reactions by high-performance liquid chromatography as indicator of P450 identity and function. Methods Enzymol. 1991; 206: 454–462
   PubMed Web of Science ®Google Scholar
• Arndt P., Volk C., Gorboulev V., Budiman T., Popp C., Ulzheimer-Teuber I., Akhoundova A., Koppatz S., Bamberg E., Nagel G., Koepsell H. Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am. J. Physiol. Renal Physiol. 2001; 281(3)F454–468
   PubMed Web of Science ®Google Scholar
• Austin R. P., Barton P., Mohmed S., Riley R. J. The binding of drugs to hepatocytes and its relationship to physicochemical properties. Drug Metab. Dispos. 2005; 33: 419–425
   PubMed Web of Science ®Google Scholar
• Avital I., Inderbitzin D., Aoki T., Tyan D. B., Cohen A. H., Ferraresso C., Rozga J., Arnaout W. S., Demetriou A. A. Isolation, characterization, and transplantation of bone marrow-derived hepatocyte stem cells. Biochem. Biophys. Res. Commun. 2001; 288(1)156–164
   PubMed Web of Science ®Google Scholar
• Bachmann K., Byers J., Ghosh R. Prediction of in vivo hepatic clearance from in vitro data using cryopreserved human hepatocytes. Xenobiotica 2003; 33(5)475–483
   PubMed Web of Science ®Google Scholar
• Bakke O. M., Manocchia M., de Abajo F., Kaitin K. I., Lasagna L. Drug safety discontinuations in the United Kingdom, the United States, and Spain from 1974 through 1993: a regulatory perspective. Clin. Pharmacol. Ther. 1995; 58(1)108–117
   PubMed Web of Science ®Google Scholar
• Bayliss M. K., Bell J. A., Jenner W. N., Park G. R., Wilson K. Utility of hepatocytes to model species differences in the metabolism of loxtidine and to predict pharmacokinetic parameters in rat, dog and man. Xenobiotica 1999; 29(3)253–268
   PubMed Web of Science ®Google Scholar
• Beerheide W., von Mach M. A., Ringel M., Fleckenstein C., Schumann S., Renzing N., Hildebrandt A., Brenner W., Jensen O., Gebhard S., Reifenberg K., Bender J., Oesch F., Hengstler J. G. Downregulation of beta2-microglobulin in human cord blood somatic stem cells after transplantation into livers of SCID-mice: an escape mechanism of stem cells?. Biochem. Biophys. Res. Commun. 2002; 294(5)1052–1063
   PubMed Web of Science ®Google Scholar
• Begue J. M., Le Bigot J. F., Guguen-Guillouzo C., Kiechel J. R., Guillouzo A. Cultured human adult hepatocytes: a new model for drug metabolism studies. Biochem. Pharmacol. 1983; 32(10)1643–1646
   PubMed Web of Science ®Google Scholar
• Benet L. Z., Spahn-Langguth H., Iwakawa S., Volland C., Mizuma T., Mayer S., Mutschler E., Lin E. T. Predictability of the Covalent Binding of Acidic Drugs in Man. Life Sci. 1993; 53(8)L141–L146
   PubMed Web of Science ®Google Scholar
• Biermann J., Lang D., Gorboulev V., Koepsell H., Sindic A., Schroter R., Zvirbliene A., Pavenstadt H., Schlatter E., Ciarimboli G. Characterization of regulatory mechanisms and states of human organic cation transporter 2. Am. J. Physiol. Cell Physiol. 2006; 290(6)C1521–1531
   PubMed Web of Science ®Google Scholar
• Bjorge S. M., Baillie T. A. Inhibition of medium-chain fatty acid beta-oxidation in vitro by valproic acid and its unsaturated metabolite, 2-n-propyl-4-pentenoic acid. Biochem. Biophys. Res. Commun. 1985; 132(1)245–252
   PubMed Web of Science ®Google Scholar
• Bjornsson T. D., Callaghan J. T., Einolf H. J., Fischer V., Gan L., Grimm S., Kao J., King S. P., Miwa G., Ni L., Kumar G., McLeod J., Obach S. R., Roberts S., Roe A., Shah A., Snikeris F., Sullivan J. T., Tweedie D., Vega J. M., Walsh J., Wrighton S. A. Pharmaceutical Research and Manufacturers of America Drug Metabolism/Clinical Pharmacology Technical Working Groups. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J. Clin. Pharmacol. 2003; 43(5)443–469
   PubMed Web of Science ®Google Scholar
• Blanchard N., Richert L., Notter B., Delobel F., David P., Coassolo P., Lave T. Impact of serum on clearance predictions obtained from suspensions and primary cultures of rat hepatocytes. Eur. J. Pharm. Sci. 2004; 23(2)189–199
   PubMed Web of Science ®Google Scholar
• Blanchard N., Alexandre E., Abadie C., Lave T., Heyd B., Mantion G., Jaeck D., Richert L., Coassolo P. Comparison of clearance predictions using primary cultures and suspensions of human hepatocytes. Xenobiotica 2005; 35(1)1–15
   PubMed Web of Science ®Google Scholar
• Blanchard N., Hewitt N. J., Silber P., Jones H., Coassolo P., Lave T. Prediction of hepatic clearance using cryopreserved human hepatocytes: a comparison of serum and serum-free incubations. J. Pharm. Pharmacol. 2006; 58(5)633–641
   PubMed Web of Science ®Google Scholar
• Bock K. W., Lipp H. P., Bock-Hennig B. S. Induction of drug-metabolizing enzymes by xenobiotics. Xenobiotica 1990; 20(11)1101–1111
   PubMed Web of Science ®Google Scholar
• Boess F., Kamber M., Romer S., Gasser R., Muller D., Albertini S., Suter L. Gene expression in two hepatic cell lines, cultured primary hepatocytes, and liver slices compared to the in vivo liver gene expression in rats: possible implications for toxicogenomics use of in vitro systems. Toxicol. Sci. 2003; 73(2)386–402
   PubMed Web of Science ®Google Scholar
• Bolze S., Bromet N., Gay-Feutry C., Massiere F., Boulieu R., Hulot T. Development of an in vitro screening model for the biosynthesis of acyl glucuronide metabolites and the assessment of their reactivity toward human serum albumin. Drug Metab. Dispos. 2002; 30(4)404–413
   PubMed Web of Science ®Google Scholar
• Bort R., Ponsoda X., Carrasco E., Gómez-Lechón M. J., Castell J. V. Metabolism of aceclofenac in humans. Drug Metab. Dispos. 1996a; 24: 834–840
   PubMed Web of Science ®Google Scholar
• Bort R., Ponsoda X., Carrasco E., Gómez-Lechón M. J., Castell J. V. Comparative metabolism of nonsteroidal antiinflamatory drug, aceclofenac, in the rat, monkey, and human. Drug Metab. Dispos. 1996b; 24: 969–975
   PubMed Web of Science ®Google Scholar
• Bort R., Gomez-Lechon M. J., Castell J. V. Jover R. Role of hepatocyte nuclear factor 3 gamma in the expression of human CYP2C genes. Arch. Biochem. Biophys. 2004; 426(1)63–72
   PubMed Web of Science ®Google Scholar
• Brown H. S., Griffin M., Houston J. B. Evaluation of cryopreserved human hepatocytes as an alternative in vitro system to microsomes for the prediction of metabolic clearance. Drug metab. Dispos. 2006; 200: 6, Nov 28; [Epub ahead of print]
   Google Scholar
• Burke M. D., Thompson S., Elcombe C. R., Halpert J., Haaparanta T., Mayer R. T. Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P-450. Biochem. Pharmacol. 1985; 34(18)3337–3345
   PubMed Web of Science ®Google Scholar
• Carmo H., Hengstler J. G., de Boer D., Ringel M., Remiao F., Carvalho F., Fernandes E., dos Reys L. A., Oesch F., de Lourdes Bastos M. Metabolic pathways of 4-bromo-2,5-dimethoxyphenethylamine (2C-B): analysis of phase I metabolism with hepatocytes of six species including human. Toxicology 2006; 206(1)75–89
   Web of Science ®Google Scholar
• Castell J. V., Hernandez D., Gomez-Foix A. M., Guillen I., Donato T., Gomez-Lechon M. J. Adenovirus-mediated gene transfer into human hepatocytes: analysis of the biochemical functionality of transduced cells. Gene Ther. 1997a; 4(5)455–464
   PubMed Web of Science ®Google Scholar
• Castell J. V., Gómez-Lechón M. J., Ponsoda X., Bort R. In vitro investigation of the molecular mechanisms of hepatotoxicity. In vitro methods in pharmaceutical research, J. V. Castell, M. J. Gómez-Lechón. Academic Press, London 1997b; 375–432
   Google Scholar
• Chandra P., Brouwer K. L. R. The complexities of hepatic drug transport: current knowledge and emerging concepts. Pharm. Res. 2004; 5: 719–735
   Web of Science ®Google Scholar
• Chauret N., Gauthier A., Nicoll-Griffith D. A. Effect of common organic solvents on in vitro cytochrome P450-mediated metabolic activities in human liver microsomes. Drug Metab. Dispos. 1998; 26(1)1–4
   PubMed Web of Science ®Google Scholar
• Chesne C., Guillouzo A. Cryopreservation of isolated rat hepatocytes: a critical evaluation of freezing and thawing conditions. Cryobiology 1988; 25(4)323–330
   PubMed Web of Science ®Google Scholar
• Chieli E., Santoni-Rugiu E., Cervelli F., Sabbatini A., Petrini M., Romiti N., Paolicchi A., Tongiani R. Differential modulation of P-glycoprotein expression by dexamethasone and 3-methylcholanthrene in rat hepatocyte primary cultures. Carcinogenesis 1994; 15(2)335–341
   PubMed Web of Science ®Google Scholar
• Chung J. Y., Cho J. Y., Yu K. S., Kim J. R., Jung H. R., Lim K. S., Jang I. J., Shin S. G. Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and drug interactions of intravenous lorazepam in healthy volunteers. Clin. Pharmacol. Ther. 2005; 77(6)486–494
   PubMed Web of Science ®Google Scholar
• Code E. L., Crespi C. L., Penman B. W., Gonzalez F. J., Chang T. K., Waxman D. J. Human cytochrome P4502B6: interindividual hepatic expression, substrate specificity, and role in procarcinogen activation. Drug Metab. Dispos. 1997; 25(8)985–993
   PubMed Web of Science ®Google Scholar
• Coffman B. L., Kearney W. R., Green M. D., Lowery R. G., Tephly T. R. Analysis of opioid binding to UDP-glucuronosyltransferase 2B7 fusion proteins using nuclear magnetic resonance spectroscopy. Mol. Pharmacol. 2001; 59: 1464–1469
   PubMed Web of Science ®Google Scholar
• Corlu A., Kneip B., Lhadi C., Leray G., Glaise D., Baffet G., Bourel D., Guguen-Guillouzo C. A plasma membrane protein is involved in cell contact-mediated regulation of tissue-specific genes in adult hepatocytes. J. Cell. Biol. 1991; 115(2)505–515
   PubMed Web of Science ®Google Scholar
• Cui Y., Konig J., Keppler D. Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2. Mol. Pharmacol. 2001; 60(5)934–943
   PubMed Web of Science ®Google Scholar
• Curi-Pedrosa R., Daujat M., Pichard L., Ourlin J. C., Clair P., Gervot L., Lesca P., Domergue J., Joyeux H., Fourtanier G., et al. Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture. J. Pharmacol. Exp. Ther. 1994; 269(1)384–392
   PubMed Web of Science ®Google Scholar
• Dai Y., Rashba-Step J., Cederbaum A. I. Stable expression of human cytochrome P4502E1 in HepG2 cells: characterization of catalytic activities and production of reactive oxygen intermediates. Biochemistry 1993; 32(27)6928–6937
   PubMed Web of Science ®Google Scholar
• Dambach D. M., Andrews B. A., Moulin F. New technologies and screening strategies for hepatotoxicity: use of in vitro models. Toxicol. Pathol. 2005; 33: 17–26
   PubMed Web of Science ®Google Scholar
• Daujat M., Peryt B., Lesca P., Fourtanier G., Domergue J., Maurel P. Omeprazole, an inducer of human CYP1A1 and 1A2, is not a ligand for the Ah receptor. Biochem. Biophys. Res. Commun. 1992; 188(2)820–825
   PubMed Web of Science ®Google Scholar
• Davies B, Morris T. Physiological parameters in laboratory animals and humans. Pharm. Res. 1993; 10(7)1093–1095
   PubMed Web of Science ®Google Scholar
• De Loecker P., Fuller B. J., Koptelov V. A., De Loecker W. Metabolic activity of freshly prepared and cryopreserved hepatocytes in monolayer culture. Cryobiology 1993; 30(1)12–18
   PubMed Web of Science ®Google Scholar
• de Longueville F., Atienzar F. A., Marcq L., Dufrane S., Evrard S., Wouters L., Leroux F., Bertholet V., Gerin B., Whomsley R., Arnould T., Remacle J., Canning M. Use of a low-density microarray for studying gene expression patterns induced by hepatotoxicants on primary cultures of rat hepatocytes. Toxicol. Sci. 2003; 75(2)378–392
   PubMed Web of Science ®Google Scholar
• de Letter E. A., Bouche M. P., Bocxlaer J. F. V., Lambert W. E., Piette M. H. Interpretation of a 3,4-methylenedioxymethamphetamine (MDMA) blood level: discussion by means of a distribution study in two fatalities. Forensic Sci. Int. 2004; 141: 85–90
   PubMed Web of Science ®Google Scholar
• Diaz D., Fabre I., Daujat M., Saint Aubert B., Bories P., Michel H., Maurel P. Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. Gastroenterology 1990; 99(3)737–747
   PubMed Web of Science ®Google Scholar
• Dilger K., Hofmann U., Klotz U. Enzyme induction in the elderly: effect of rifampin on the pharmacokinetics and pharmacodynamics of propafenone. Clin. Pharmacol. Ther. 2000; 67(5)512–520
   PubMed Web of Science ®Google Scholar
• Dodds P. F. Xenobiotic lipids: the inclusion of xenobiotic compounds in pathways of lipid biosynthesis. Prog. Lipid Res. 1995; 34(3)219–247
   PubMed Web of Science ®Google Scholar
• Donato M. T., Castell J. V., Gómez-Lechón M. J. Effect of model inducers on cytochrome P450 activities of human hepatocytes in primary cultures. Drug Metab. Disp. 1995; 23: 553–558
   PubMed Web of Science ®Google Scholar
• Donato M. T., Castell J. V. G, ómez-Lechón M. J. Characterization of drug metabolizing activities in pig hepatocytes for use in bioartificial liver devices. Comparison with other hepatic cellular models. J. Hepatol. 1999; 31: 542–549
   PubMed Web of Science ®Google Scholar
• Doyle L. A., Ross D. D. Multidrug resistance mediated by the breast cancer resistance protein BCRP(ABCG2). Oncogene 2003; 22: 7340–7358
   PubMed Web of Science ®Google Scholar
• Drew R., Knights K. Postulated reactive intermediates of NSAID's. Agents Actions Suppl. 1985; 17: 127–133
   PubMedGoogle Scholar
• Drocourt L., Pascussi J. M., Assenat E., Fabre J. M., Maurel P., Vilarem M. J. Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Drug Metab. Dispos. 2001; 29(10)1325–1331
   PubMed Web of Science ®Google Scholar
• Dunn J. C., Tompkins R. G., Yarmush M. L. Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration. Biotechnol. Prog. 1991; 7(3)237–245
   PubMed Web of Science ®Google Scholar
• Easterbrook J., Lu C., Sakai Y., Li A. P. Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes. Drug Metab. Dispos. 2001; 29(2)141–144
   PubMed Web of Science ®Google Scholar
• Eberhardt M., Salmon P., von Mach M. A., Hengstler J. G., Brulport M., Linscheid P., Seboek D., Oberholzer J., Barbero A., Martin I., Muller B., Trono D., Zulewski H. Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Biochem. Biophys. Res. Commun. 2006; 345(3)1167–1176
   PubMed Web of Science ®Google Scholar
• Ekins S., Wrighton S. A. The role of CYP2B6 in human xenobiotic metabolism. Drug Metab. Rev. 1999; 31(3)719–754
   PubMed Web of Science ®Google Scholar
• Elferink M. G., Olinga P., Draaisma A. L., Merema M. T., Faber K. N., Slooff M. J., Meijer D. K., Groothuis G. M. LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process. Am. J. Physiol. Gastrointest. Liver. Physiol. 2004; 287(5)G1008–G1016
   Web of Science ®Google Scholar
• Ellinger-Ziegelbauer H., Stuart B., Wahle B., Bomann W., Ahr H. J. Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver. Mutat. Res. 2005; 575: 61–84
   PubMed Web of Science ®Google Scholar
• Emoto C., Yamazaki H., Yamasaki S., Shimada N., Nakajima M., Yokoi T. Characterization of cytochrome P450 enzymes involved in drug oxidations in mouse intestinal microsomes. Xenobiotica 2000; 30(10)943–953
   PubMed Web of Science ®Google Scholar
• Eneroth A., Vrang L., Astner L., Sahlberg B. L., Hewitt N. J. Clearance studies using cryopreserved pooled human (LiverPool™) hepatocytes:reproducibility within one lot and between lots. Drug Metab. Rev. 2006; 38(1)61–62
   Google Scholar
• Engtrakul J. J., Foti R. S., Strelevitz T. J., Fisher M. B. Altered AZT (3′-deoxythymidine) glucuronidation kinetics in liver microsomes as an explanation for underprediction of in vivo clearance; comparison to hepatocytes and effect of incubation environment. Drug Metab. Dispos. 2005; 33: 1621–1627
   PubMed Web of Science ®Google Scholar
• Fardel O., Lecureur V., Guillouzo A. Regulation by dexamethasone of P-glycoprotein expression in cultured rat hepatocytes. FEBS Lett. 1993; 327(2)189–193
   PubMed Web of Science ®Google Scholar
• Farkas D., Tannenbaum S. R. In vitro methods to study chemically-induced hepatotoxicity: a literature. Curr. Drug Metab. 2005; 6: 111–125
   PubMed Web of Science ®Google Scholar
• Faucette S. R., Hawke R. L., Lecluyse E. L., Shord S. S., Yan B., Laethem R. M., Lindley C. M. Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. Drug Metab. Dispos. 2000; 28(10)1222–1230
   PubMed Web of Science ®Google Scholar
• Faucette S. R., Wang H., Hamilton G. A., Jolley S. L., Gilbert D., Lindley C., Yan B., Negishi M., LeCluyse E. L. Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab. Dispos. 2004; 32(3)348–358
   PubMed Web of Science ®Google Scholar
• Fautrel A., Joly B., Guyomard C., Guillouzo A. Long-term maintenance of drug-metabolizing enzyme activities in rat hepatocytes after cryopreservation. Toxicol. Appl. Pharmacol. 1997; 147(1)110–114
   PubMed Web of Science ®Google Scholar
• Favreau L. V., Palamanda J. R., Lin C. C, Nomeir A. A. Improved reliability of the rapid microtiter plate assay using recombinant enzyme in predicting CYP2D6 inhibition in human liver microsomes. Drug Metab. Dispos. 1999; 27(4)436–439
   PubMed Web of Science ®Google Scholar
• Fella K., Gluckmann M., Hellmann J., Karas M., Kramer P. J., Kroger M. Use of two-dimensional gel electrophoresis in predictive toxicology: identification of potential early protein biomarkers in chemically induced hepatocarcinogenesis. Proteomics. 2005; 5(7)1914–1927
   PubMed Web of Science ®Google Scholar
• Ferguson P. L., Smith R. D. Proteome analysis by mass spectrometry. Annu. Rev. Biophys. Biomol. Struct. 2003; 32: 399–424
   PubMedGoogle Scholar
• Ferrini J. B., Pichard I., Domergue J., Maurel P. Long-term primary cultures of adult human hepatocytes. Chem. Biol. Interact. 1997; 107: 31–45
   PubMed Web of Science ®Google Scholar
• Fiegel H. C., Lioznov M. V., Cortes-Dericks L., Lange C., Kluth D., Fehse B., Zander A. R. Liver-specific gene expression in cultured human hematopoietic stem cells. Stem Cells. 2003; 21: 98–104
   PubMed Web of Science ®Google Scholar
• Fisher M. B., Yoon K., Vaughn M. L., Strelevitz T. J., Foti R. S. Flavin-containing monooxygenase activity in hepatocytes and microsomes: in vitro characterization and in vivo scaling of benzydamine clearance. Drug Metab. Dispos. 2002; 30(10)1087–1093
   PubMed Web of Science ®Google Scholar
• Fromenty B., Pessayre D. Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity. Pharmacol. Ther. 1995; 67(1)101–154
   PubMed Web of Science ®Google Scholar
• Fuhr U. Induction of drug metabolising enzymes: pharmacokinetic and toxicological consequences in humans. Clin. Pharmacokinet 2000; 38(6)493–504
   PubMed Web of Science ®Google Scholar
• Galisteo M., Marc N., Fautrel A., Guillouzo A., Corcos L., Lagadic-Gossmann D. Involvement of cyclic nucleotide- and calcium-regulated pathways in phenobarbital-induced cytochrome P-450 3A expression in mouse primary hepatocytes. J. Pharmacol. Exp. Ther. 1999; 290(3)1270–1277
   PubMed Web of Science ®Google Scholar
• Garcia M., Rager J., Wang Q., Strab R., Hidalgo I. J., Owen A., Li J. Cryopreserved human hepatocytes as alternative in vitro model for cytochrome p450 induction studies. In Vitro Cell Dev. Biol. Anim. 2003; 39(7)283–287
   PubMed Web of Science ®Google Scholar
• Gardner-Stephen D., Heydel J. M., Goyal A., Lu Y., Xie W., Lindblom T., Mackenzie P., Radominska-Pandya A. Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression. Drug Metab. Dispos. 2004; 32(3)340–347
   PubMed Web of Science ®Google Scholar
• Gerbal-Chaloin S., Pascussi J. M., Pichard-Garcia L., Daujat M., Waechter F., Fabre J. M., Carrere N., Maurel P. Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab. Dispos. 2001; 29(3)242–251
   PubMed Web of Science ®Google Scholar
• Gerbal-Chaloin S., Daujat M., Pascussi J. M., Pichard-Garcia L., Vilarem M. J., Maurel P. Transcriptional regulation of CYP2C9 gene. Role of glucocorticoid receptor and constitutive androstane receptor. J. Biol. Chem. 2002; 277(1)209–217
   PubMed Web of Science ®Google Scholar
• Gerbal-Chaloin S., Pichard-Garcia L., Fabre J. M., Sa-Cunha A., Poellinger L., Maurel P., Daujat-Chavanieu M. Role of CYP3A4 in the regulation of the aryl hydrocarbon receptor by omeprazole sulphide. Cell Signal 2006; 18(5)740–750
   PubMed Web of Science ®Google Scholar
• Gitlin N., Julie N. L., Spurr C. L., Lim K. N., Juarbe H. M. Two cases of severe clinical and histologic hepatotoxicity associated with troglitazone. Ann. Intern. Med. 1998; 129(1)36–38
   PubMed Web of Science ®Google Scholar
• Gomez-Lechon M. J., Donato T., Ponsoda X., Castell J. V. Human hepatic cell cultures: in vitro and in vivo drug metabolism. Altern. Lab. Anim. 2003; 31(3)257–265
   PubMed Web of Science ®Google Scholar
• Gomez-Lechon M. J., Donato M. T., Castell J. V., Jover R. Human hepatocytes in primary culture: the choice to investigate drug metabolism in man. Curr. Drug Metab. 2004; 5(5)443–462
   PubMed Web of Science ®Google Scholar
• Goodwin B., Hodgson E., Liddle C. The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol. Pharmacol. 1999; 56(6)1329–1339
   PubMed Web of Science ®Google Scholar
• Goodwin B., Redinbo M. R., Kliewer S. A. Regulation of cyp3a gene transcription by the pregnane x receptor. Annu. Rev. Pharmacol. Toxicol. 2002; 42: 1–23
   PubMed Web of Science ®Google Scholar
• Grant M. H., Melvin M. A., Shaw P., Melvin W. T., Burke M. D. Studies on the maintenance of cytochromes P-450 and b5, monooxygenases and cytochrome reductases in primary cultures of rat hepatocytes. FEBS Lett. 1985; 190(1)99–103
   PubMed Web of Science ®Google Scholar
• Green A. R. MDMA: fact and fallacy, and the need to increase knowledge in both the scientific and popular press. Psychopharmacology 2004; 173: 231–233
   PubMed Web of Science ®Google Scholar
• Griffin S. J., Houston J. B. Prediction of in vitro intrinsic clearance from hepatocytes: comparison of suspensions and monolayer cultures. Drug Metab. Dispos. 2005; 33(1)115–120
   PubMed Web of Science ®Google Scholar
• Grillo M. P., Chiellini G., Tonelli M., Benet L. Z. Effect of alpha-fluorination of valproic acid on valproyl-S-acyl-CoA formation in vivo in rats. Drug Metab. Dispos. 2001; 29(9)1210–1215
   PubMed Web of Science ®Google Scholar
• Grillo M. P., Benet L. Z. Studies on the reactivity of clofibryl-S-acyl-CoA thioester with glutathione in vitro. Drug Metab. Dispos. 2002; 30(1)55–62
   PubMed Web of Science ®Google Scholar
• Grillo M. P., Knutson C. G., Sanders P. E., Waldon D. J., Hua F., Ware J. A. Studies on the chemical reactivity of diclofenac acyl glucuronide with glutathione: identification of diclofenac-S-acyl-glutathione in rat bile. Drug Metab. Dispos. 2003; 31(11)1327–1336
   PubMed Web of Science ®Google Scholar
• Gripon P., Rumin S., Urban S., Le Seyec J., Glaise D., Cannie I., Guyomard C., Lucas J., Trepo C., Guguen-Guillouzo C. Infection of a human hepatoma cell line by hepatitis B virus. Proc. Natl. Acad. Sci. U.S.A. 2002; 99(24)15655–15660
   PubMed Web of Science ®Google Scholar
• Guengerich F. P, Shimada T., Iwasaki M., Butler M. A., Kadlubar F. F. Activation of carcinogens by human liver cytochromes P-450. Basic Life Sci. 1990; 53: 381–396
   PubMedGoogle Scholar
• Guguen-Guillouzo C., Clement B., Baffet G., Beaumont C., Morel-Chany E., Glaise D., Guillouzo A. Maintenance and reversibility of active albumin secretion by adult rat hepatocytes co-cultured with another liver epithelial cell type. Exp. Cell Res. 1983; 143(1)47–54
   PubMed Web of Science ®Google Scholar
• Guillouzo A., Chesne C. Xenobiotic metabolism in epithelial cell cultures. Epithelial Cell Culture, A Practical Approach, A. J. Shaw AJ. Oxford University Press, London 1996; 67–85
   Google Scholar
• Guillouzo A., Morel F., Langouet S., Maheo K., Rissel M. Use of hepatocyte cultures for the study of hepatotoxic compounds. J. Hepatol. 1997; 26: 73–80
   PubMed Web of Science ®Google Scholar
• Guilouzo A. Liver cell models in in vitro toxicology. Environ. Health Perspect 1998; 106(suppl. 2)511–532
   Google Scholar
• Guyomard C., Rialland L., Fremond B., Chesne C., Guillouzo A. Influence of alginate gel entrapment and cryopreservation on survival and xenobiotic metabolism capacity of rat hepatocytes. Toxicol. Appl. Pharmacol. 1996; 141: 349–356
   PubMed Web of Science ®Google Scholar
• Hallifax D., Rawden H. C., Hazook N., Houston J. B. Prediction of metabolic clearance using cryopreserved human hepatocytes: kinetic characteristics for five benzodiazepines. Drug Metab. Dispos. 2005; 33: 1852–1858
   PubMed Web of Science ®Google Scholar
• Hallifax D., Houston J. B. Uptake and intracellular binding of lipophilic amine drugs by isolated rat hepatocytes and implications for prediction of in vivo metabolic clearance. Drug Metab. Dispos. 2006, Aug 1; [Epub ahead of print].
   Web of Science ®Google Scholar
• Hamilton G. A., Jolley S. L., Gilbert D., Coon D. J., Barros S., LeCluyse E. L. Regulation of cell morphology and cytochrome P450 expression in human hepatocytes by extracellular matrix and cell-cell interactions. Cell Tissue Res. 2001; 306(1)85–99
   PubMed Web of Science ®Google Scholar
• Hanna I. H., Reed J. R., Guengerich F. P., Hollenberg P. F. Expression of human cytochrome P450 2B6 in Escherichia coli: characterization of catalytic activity and expression levels in human liver. Arch. Biochem. Biophys. 2000; 376(1)206–216
   PubMed Web of Science ®Google Scholar
• Harauchi T., Hirata M. Effect of P-450 inducers on glutathione (GSH) depletion by bromobenzene in primary cultures of dog hepatocytes. Biol. Pharm. Bull. 1994; 17(5)658–661
   PubMed Web of Science ®Google Scholar
• Hargus S. J., Amouzedeh H. R., Pumford N. R., Myers T. G., McCoy S. C., Pohl L. R. Metabolic activation and immunochemical localization of liver protein adducts of the nonsteroidal anti-inflammatory drug diclofenac. Chem. Res. Toxicol. 1994; 7(4)575–582
   PubMed Web of Science ®Google Scholar
• Hargus S. J., Martin B. M., George J. W., Pohl L. R. Covalent modification of rat liver dipeptidyl peptidase IV (CD26) by the nonsteroidal anti-inflammatory drug diclofenac. Chem. Res. Toxicol. 1995; 8(8)993–996
   PubMed Web of Science ®Google Scholar
• Hariparsad N., Nallani S. C., Sane R. S., Buckley D. J., Buckley A. R., Desai P. B. Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital. J. Clin. Pharmacol. 2004; 44(11)1273–1281
   PubMed Web of Science ®Google Scholar
• Harris A. J., Dial S. L., Casciano D. A. Comparison of basal gene expression profiles and effects of hepatocarcinogens on gene expression in cultured primary human hepatocytes and HepG2 cells. Mutat. Res. 2004; 549(1–2)79–99
   PubMed Web of Science ®Google Scholar
• Haskins J. R., Rowse P., Rahbari R., de la Iglesia F. A. Thiazolidinedione toxicity to isolated hepatocytes revealed by coherent multiprobe fluorescence microscopy and correlated with multiparameter flow cytometry of peripheral leukocytes. Arch. Toxicol. 2001; 75(7)425–438
   PubMed Web of Science ®Google Scholar
• He K., Talaat R. E., Pool W. F., Reily M. D., Reed J. E., Bridges A. J., Woolf T. F. Metabolic activation of troglitazone: identification of a reactive metabolite and mechanisms involved. Drug Metab. Dispos. 2004; 32(6)639–646
   PubMed Web of Science ®Google Scholar
• Hengstler J. G., Utesch D., Steinberg P., Platt K. L., Diener B., Ringel M., Swales N., Fischer T., Biefang K., Gerl M., Bottger T., Oesch F. Drug Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction. Metab. Rev. 2000; 32(1)81–118
   PubMed Web of Science ®Google Scholar
• Hengstler J. G., Bogdanffy M. S., Bolt H. M., Oesch F. Challenging Dogma: Thresholds for Genotoxic Carcinogens? The case of Vinyl Acetate. Annu. Rev. Pharmacol. Toxicol. 2003; 43: 485–520
   PubMed Web of Science ®Google Scholar
• Hengstler J. G., Brulport M., Schormann W., Bauer A., Hermes M., Nussler A. K., Fandrich F., Ruhnke M., Ungefroren H., Griffin L., Bockamp E., Oesch F., von Mach M.-A. Generation of human hepatocytes by stem cell technology: definition of the hepatocyte. Expert Opin. Drug Metab. Toxicol. 2005; 1: 61–74
   PubMedGoogle Scholar
• Hengstler J. G., Brulport M., Schormann W., Bauer A., Hermes M., Nussler A. K., Fandrich F., Ruhnke M., Ungefroren H., Griffin L., Bockamp E., Oesch F., von Mach M.-A. Generation of human hepatocytes by stem cell technology: definition of the hepatocyte. Expert Opin. Drug Metab. Toxicol. 2006; 1: 61–74
   Google Scholar
• Hertz R., Bar-Tana J. The acylation of proteins by xenobiotic amphipathic carboxylic acids in cultured rat hepatocytes. Biochem. J. 1988; 254(1)39–44
   PubMed Web of Science ®Google Scholar
• Hesse L. M., Venkatakrishnan K., Court M. H., von Moltke L. L., Duan S. X., Shader R. I., Greenblatt D. J. CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab. Dispos. 2000; 28(10)1176–1183
   PubMed Web of Science ®Google Scholar
• Hewitt N. J., Hewitt P. Phase I and II enzyme characterization of two sources of HepG2 cell lines. Xenobiotica 2004; 34(3)243–256
   PubMed Web of Science ®Google Scholar
• Hewitt N. J., Buhring K. U., Dasenbrock J., Haunschild J., Ladstetter B., Utesch D. Studies comparing in vivo:in vitro metabolism of three pharmaceutical compounds in rat, dog, monkey, and human using cryopreserved hepatocytes, microsomes, and collagen gel immobilized hepatocyte cultures. Drug Metab. Dispos. 2001; 29(7)1042–1050
   PubMed Web of Science ®Google Scholar
• Hewitt N. J., Lloyd S., Hayden M., Butler R., Sakai Y., Springer R., Fackett A., Li A. P. Correlation between troglitazone cytotoxicity and drug metabolic enzyme activities in cryopreserved human hepatocytes. Chem. Biol. Interact. 2002; 142(1–2)73–82
   PubMed Web of Science ®Google Scholar
• Hewitt N. J., de Kanter R., Le Cluyse E. Induction of Drug metabolizing enzymes: A survey at in vitro methodologies and interpretations used in the pharmaceutical industry. Do they comply with FDA recommendations?. Chem. Biol. Interact. In press
   Web of Science ®Google Scholar
• Hickman D., Wang J. P., Wang Y., Unadkat J. D. Evaluation of the selectivity of In vitro probes and suitability of organic solvents for the measurement of human cytochrome P450 monooxygenase activities. Drug Metab. Dispos. 1998; 26(3)207–215
   PubMed Web of Science ®Google Scholar
• Hirano M., Maeda K., Shitara Y., Sugiyama Y. Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. J. Pharmacol. Exp. Ther. 2004; 311(1)139–146
   PubMed Web of Science ®Google Scholar
• Hollenberg P. F. Characteristics and common properties of inhibitors, inducers, and activators of CYP enzymes. Drug Metab. Rev. 2002; 34(1–2)17–35
   PubMed Web of Science ®Google Scholar
• Hopwood J., Quigley A., Eagle C., Powell H., Eakins J., Kenna J. G. Are primary rat hepatocyte cultures appropriate for predictive hepatotoxicity testing of pharmaceuticals?. Toxicology 2004; 202(1–2)103–104
   Web of Science ®Google Scholar
• Houston J. B. Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance. Biochem. Pharmacol. 1994; 47(9)1469–1479
   PubMed Web of Science ®Google Scholar
• Houston J. B., Carlile D. J. Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. Drug Metab. Rev. 1997; 29(4)891–922
   PubMed Web of Science ®Google Scholar
• Huang Q., Jin X., Gaillard E. T., Knight B. L., Pack F. D., Stoltz J. H., Jayadev S., Blanchard K. T. Gene expression profiling reveals multiple toxicity end points induced by hepatotoxicants. Mutat Res. 2004; 549: 147–167
   PubMed Web of Science ®Google Scholar
• Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 2005; 5(1)6–13
   PubMed Web of Science ®Google Scholar
• Ito K., Houston J. B. Comparison of the use of liver models for prediction of drug clearance using in vitro kinetic data from hepatic microsomes and isolated hepatocytes. Pharm. Res. 2004; 21: 785–792
   PubMed Web of Science ®Google Scholar
• Ito K., Houston J. B. Prediction of human drug clearance from in vitro and preclinical data using physiologically based and empirical approaches. Pharm. Res. 2005; 22: 103–112
   PubMed Web of Science ®Google Scholar
• Iwatsubo T., Hirota N., Ooie T., Suzuki H., Shimada N., Chiba K., Ishizaki T., Green C. E., Tyson C. A., Sugiyama Y. Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data. Pharmacol. Ther. 1997; 73(2)147–171
   PubMed Web of Science ®Google Scholar
• Jang Y. Y., Collector M. I., Baylin S. B., Diehl A. M., Sharkis S. J. Hematopoietic stem cells convert into liver cells within days without fusion. Nat. Cell Biol. 2004; 6: 532–539
   PubMed Web of Science ®Google Scholar
• Jiang Y., Jahagirdar B. N., Reinhardt R. L., Schwartz R. E., Keene C. D., Ortiz-Gonzalez X. R., Reyes M., Lenvik T., Lund T., Blackstad M., Du J., Aldrich S., Lisberg A., Low W. C., Largaespada D. A., Verfaillie C. M. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41–49
   PubMed Web of Science ®Google Scholar
• Jones H. M., Hallifax D., Houston J. B. Quantitative prediction of the in vivo inhibition of diazepam metabolism by omeprazole using rat liver microsomes and hepatocytes. Drug Metab. Dispos. 2004; 32: 572–580
   PubMed Web of Science ®Google Scholar
• Jones H. M., Nicholls G., Houston J. B. Impact of end-product inhibition on the determination of in vitro metabolic clearance. Xenobiotica 2005; 35: 439–454
   PubMed Web of Science ®Google Scholar
• Jover R., Bort R., Gomez-Lechon M. J., Castell J. V. Re-expression of C/EBP alpha induces CYP2B6, CYP2C9 and CYP2D6 genes in HepG2 cells. FEBS Lett. 1998; 431(2)227–230
   PubMed Web of Science ®Google Scholar
• Jover R., Bort R., Gomez-Lechon M. J., Castell J. V. Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: a study using adenovirus-mediated antisense targeting. Hepatology 2001; 33(3)668–675
   PubMed Web of Science ®Google Scholar
• Jover R., Bort R., Gomez-Lechon M. J., Castell J. V. Down-regulation of human CYP3A4 by the inflammatory signal interleukin-6: molecular mechanism and transcription factors involved. FASEB J. 2002; 16(13)1799–1801
   PubMed Web of Science ®Google Scholar
• Kafert-Kasting S., Alexandrova K., Barthold M., Laube B., Friedrich G., Arseniev L., Hengstler J. G. Enzyme induction in cryopreserved human hepatocyte cultures. Toxicology 2006; 220(2–3)117–125
   PubMed Web of Science ®Google Scholar
• Kamiya A., Inoue Y., Gonzalez F. J. Role of the hepatocyte nuclear factor 4alpha in control of the pregnane X receptor during fetal liver development. Hepatology 2003; 37(6)1375–1384
   PubMed Web of Science ®Google Scholar
• Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat. Rev. Drug Discov. 2005; 4(6)489–499
   PubMed Web of Science ®Google Scholar
• Kassahun K., Hu P., Grillo M. P., Davis M. R., Jin L., Baillie T. A. Metabolic activation of unsaturated derivatives of valproic acid. Identification of novel glutathione adducts formed through coenzyme A-dependent and -independent processes. Chem. Biol. Interact. 1994; 90(3)253–275
   PubMed Web of Science ®Google Scholar
• Kato M., Chiba K., Horikawa M., Sugiyama Y. The quantitative prediction of in vivo enzyme-induction caused by drug exposure from in vitro information on human hepatocytes. Drug Metab. Pharmacokinet 2005; 20(4)236–243
   PubMedGoogle Scholar
• Kawana K., Ikuta T., Kobayashi Y., Gotoh O., Takeda K., Kawajiri K. Molecular mechanism of nuclear translocation of an orphan nuclear receptor, SXR. Mol. Pharmacol. 2003; 63(3)524–531
   PubMed Web of Science ®Google Scholar
• Kern A., Bader A., Pichlmayr R., Sewing K. F. Drug metabolism in hepatocyte sandwich cultures of rats and humans. Biochem. Pharmacol. 1997; 54(7)761–772
   PubMed Web of Science ®Google Scholar
• Kim R. B., Leake B. F., Choo E. F., Dresser G. K., Kubba S. V., Schwarz U. I., Taylor A., Xie H. G., McKinsey J., Zhou S., Lan L. B., Schuetz J. D., Schuetz E. G., Wilkinson G. R. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin. Pharmacol. Ther. 2001; 70(2)189–199
   PubMed Web of Science ®Google Scholar
• Kim R. B. Transporters and drug discovery: why, when, and how. Mol. Pharm. 2006; 3(1)26–32
   PubMed Web of Science ®Google Scholar
• Kliewer S. A., Goodwin B., Willson T. M. The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocr. Rev. 2002; 23(5)687–702
   PubMed Web of Science ®Google Scholar
• Klingmüller U., Bauer A., Bohl S., Nickel P. J., Breitkopf K., Dooley S., Zellmer S., Kern Claudia, Merfort I., Sparna T., Donauer J., Walz G., Geyer M., Kreutz C., Hermes M., Götschel F., Hecht A., Walter D., Egger L., Neubert K., Borner C., Brulport M., Schormann W., Sauer C., Baumann F., Preiss R., MacNelly S., Godoy P., Wiercinska E., Ciuclan L., Edelmann J., Kleemann W. J., Zeilinger K., Heinrich M., Zanger U. M., Gebhardt G., Maiwald T., Heinrich R., von Weizsäcker F., Timmer J., Hengstler J. G. Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways. Systems Biology 2006, in press
   PubMedGoogle Scholar
• Kobayashi O., Sakaguchi M., Okitsu T., Totsugawa T., Maruyama M., Matsumura T., Watanabe T., Noguchi H., Kosaka Y., Fujiwara T., Tanaka N. Improvement in the differentiated hepatic phenotype of immortalized human hepatocytes by adenovirus mediated p21 gene transfer. ASAIO J. 2002a; 48(4)355–359
   PubMed Web of Science ®Google Scholar
• Kobayashi K., Urashima K., Shimada N., Chiba K. Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with cDNA-expressed systems of the rat. Biochem. Pharmacol. 2002b; 63: 889–896
   PubMed Web of Science ®Google Scholar
• Koebe H. G., Dahnhardt C., Muller-Hocker J., Wagner H., Schildberg F. W. Cryopreservation of porcine hepatocyte cultures. Cryobiology 1996; 33(1)127–141
   PubMed Web of Science ®Google Scholar
• Koebe H. G., Muhling B., Deglmann C. J., Schildberg F. W. Cryopreserved porcine hepatocyte cultures. Chem. Biol. Interact. 1999; 121(1)99–115
   PubMed Web of Science ®Google Scholar
• Koganti A., Zhang W., Cheesborough M., Terrel C. M., Silber P. M., Jensen C. B. Metabolic stability and clearance of pharmaceutical chemicals in pre-pooled cryopreserved human hepatocytes. Drug Metab. Rev. 2005; 37(2)212–213
   Google Scholar
• Kolars J. C., Turgeon D. K., Watkins P. B. Omeprazole and aryl hydrocarbon hydroxylases: should we be worried?. Hepatology 1991; 13(1)197–199
   PubMedGoogle Scholar
• Komoroski B. J., Zhang S., Cai H., Hutzler J. M., Frye R., Tracy T. S., Strom S. C., Lehmann T., Ang C. Y., Cui Y. Y., Venkataramanan R. Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures. Drug Metab. Dispos. 2004; 32(5)512–518
   PubMed Web of Science ®Google Scholar
• Koop D. R., Tierney D. J. Multiple mechanisms in the regulation of ethanol-inducible cytochrome P450IIE1. Bioessays 1990; 12(9)429–435
   PubMed Web of Science ®Google Scholar
• Kostrubsky V. E., Lewis L. D., Strom S. C., Wood S. G., Schuetz E. G., Schuetz J. D., Sinclair P. R., Wrighton S. A., Sinclair J. F. Induction of cytochrome P4503A by taxol in primary cultures of human hepatocytes. Arch. Biochem. Biophys. 1998; 355(2)131–136
   PubMed Web of Science ®Google Scholar
• Kostrubsky V. E., Ramachandran V., Venkataramanan R., Dorko K., Esplen J. E., Zhang S., Sinclair J. F., Wrighton S. A., Strom S. C. The use of human hepatocyte cultures to study the induction of cytochrome P-450. Drug Metab. Dispos. 1999; 27(8)887–894
   PubMed Web of Science ®Google Scholar
• Kostrubsky V. E., Sinclair J. F., Ramachandran V., Venkataramanan R., Wen Y. H., Kindt E., Galchev V., Rose K., Sinz M., Strom S. C. The role of conjugation in hepatotoxicity of troglitazone in human and porcine hepatocyte cultures. Drug Metab. Dispos. 2000; 28(10)1192–1197
   PubMed Web of Science ®Google Scholar
• Kostrubsky V. E., Strom S. C., Hanson J., Urda E., Rose K., Burliegh J., Zocharski P., Cai H., Sinclair J. F., Sahi J. Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats. Toxicol. Sci. 2003; 76(1)220–228
   PubMed Web of Science ®Google Scholar
• Kretz-Rommel A., Boelsterli U. A. Diclofenac covalent protein binding is dependent on acyl glucuronide formation and is inversely related to P450-mediated acute cell injury in cultured rat hepatocytes. Toxicol. Appl. Pharmacol. 1993; 120(1)155–161
   PubMed Web of Science ®Google Scholar
• Kullak-Ublick G. A, Stieger B., Meier P. J. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 2004; 126(1)322–42
   PubMed Web of Science ®Google Scholar
• Kullak-Ublick G. A., Becker M. B. Regulation of drug and bile salt transporters in liver and intestine. Drug Metab. Rev. 2003; 35(4)305–317
   PubMed Web of Science ®Google Scholar
• Kunieda T., Kobayashi N., Sakaguchi M., Okitsu T., Totsugawa T., Watanabe T., Matsumura T., Maruyama M., Noguchi H., Takesue M., Shibata N., Ohmoto K., Fujiwara T., Yamamoto S., Tanaka N. Transduction of immortalized human hepatocytes with p21 to enhance differentiated phenotypes. Cell Transplant 2002; 11(5)421–428
   PubMed Web of Science ®Google Scholar
• Kuroha M., Kuze Y., Shimoda M., Kokue E. In vitro characterization of the inhibitory effects of ketoconazole on metabolic activities of cytochrome P-450 in canine hepatic microsomes. Am. J. Vet. Res. 2002; 63: 900–905
   PubMed Web of Science ®Google Scholar
• Laishes B. A., Williams G. M. Conditions affecting primary cell cultures of functional adult rat hepatocytes. II. Dexamethasone enhanced longevity and maintenance of morphology. In Vitro. 1976; 12(12)821–832
   PubMedGoogle Scholar
• Lam J. L., Benet L. Z. Hepatic microsome studies are insufficient to characterize in vivo hepatic metabolic clearance and metabolic drug-drug interactions: studies of digoxin metabolism in primary rat hepatocytes versus microsomes. Drug Metab. Dispos. 2004; 32: 1311–1316
   PubMed Web of Science ®Google Scholar
• Lam C. M., Chan A. O., Ho P., Ng I. O., Lo C. M., Liu C. L., Poon R. T., Fan S. T. Different presentation of hepatitis B-related hepatocellular carcinoma in a cohort of 1863 young and old patients - implications for screening. Aliment. Pharmacol. Ther. 2004; 19(7)771–777
   PubMed Web of Science ®Google Scholar
• Lampe J. W., Bigler J., Horner N. K., Potter J. D. UDP-glucuronosyltransferase (UGT1A1*28 and UGT1A6*2) polymorphisms in Caucasians and Asians: relationships to serum bilirubin concentrations. Pharmacogenetics 1999; 9: 341–349
   PubMedGoogle Scholar
• Lau Y. Y., Sapidou E., Cui X., White R. E., Cheng K.-C. Development of a novel in vitro model to predict hepatic clearance using fresh, cryopreserved and sandwich-cultured hepatocytes. Drug Metab. Dispos. 2002; 30: 1446–1454
   PubMed Web of Science ®Google Scholar
• Lave T., Dupin S., Schmitt C., Valles B., Ubeaud G., Chou R. C., Jaeck D., Coassolo P. The use of human hepatocytes to select compounds based on their expected hepatic extraction ratios in humans. Pharm. Res. 1997; 14(2)152–155
   PubMed Web of Science ®Google Scholar
• Lavon N., Yanuka O. Benvenisty N. Differentiation and isolation of hepatic-like cells from human embryonic stem cells. Differentiation 2004; 72: 230–238
   PubMed Web of Science ®Google Scholar
• Lawrence J. N., Benford D. J. Development of an optimal method for the cryopreservation of hepatocytes and their subsequent monolayer culture. Toxic. In Vitro. 1991; 5(1)39–50
   PubMed Web of Science ®Google Scholar
• LeCluyse E. L., Audus K. L., Hochman J. H. Formation of extensive canalicular networks by rat hepatocytes cultured in collagen-sandwich configuration. Am. J. Physiol. 1994; 266: C1764–C1774
   PubMed Web of Science ®Google Scholar
• LeCluyse E. L., Bullock P. L., Parkinson A. Strategies for restoration and maintenance of normal hepatic structure and function in long-term cultures of rat hepatocytes. Adv. Drug Deliv. Rev. 1996a; 22: 133–186
   Web of Science ®Google Scholar
• LeCluyse E. L., Bullock P., Parkinson A., Hochman J. H. Cultured rat hepatocytcs. Model Systems for Biopharmaceutical Assessment of Drug Absorption and Metabolism, R. T. Borchardt, G. Wilson, P. Smith. Plenum Press, New York 1996b; 121–159
   Google Scholar
• LeCluyse E., Bullock P., Madan A., Carroll K., Parkinson A. Influence of extracellular matrix overlay and medium formulation on the induction of cytochrome P-450 2B enzymes in primary cultures of rat hepatocytes. Drug Metab. Dispos. 1999; 27(8)909–915
   PubMed Web of Science ®Google Scholar
• LeCluyse E. L. Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur. J. Pharmac. Sci. 2001; 13(4)343–368
   PubMed Web of Science ®Google Scholar
• Lee C. H. Differential regulation of P-glycoprotein genes in primary rat hepatocytes by collagen sandwich and drugs. J. Cell. Biochem. 2002; 86(1)12–20
   PubMed Web of Science ®Google Scholar
• Lee W. M. Drug-induced hepatotoxicity. N. Engl. J. Med. 2003; 349(5)474–485
   PubMed Web of Science ®Google Scholar
• Lee K. D., Kuo T. K., Whang-Peng J., Chung Y. F., Lin C. T., Chou S. H., Chen J. R., Chen Y. P., Lee O. K. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004; 40: 1275–1284
   PubMed Web of Science ®Google Scholar
• Lehmann J. M., McKee D. D., Watson M. A., Willson T. M., Moore J. T., Kliewer S. A. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J. Clin. Invest. 1998; 102(5)1016–1023
   PubMed Web of Science ®Google Scholar
• Li A. P., Roque M. A., Beck D. J., Kaminski D. L. Isolation and culturing of hepatocytes from human livers. J. Tiss. Cult. Meth. 1992; 14: 139–146
   Google Scholar
• Li A. P., Jurima-Romet M. Applications of primary human hepatocytes in the evaluation of pharmacokinetic drug-drug interactions: evaluation of model drugs terfenadine and rifampin. Cell Biol. Toxicol. 1997; 13(4–5)365–374
   PubMed Web of Science ®Google Scholar
• Li A. P., Hartman N. R., Lu C., Collins J. M, Strong J. M. Effects of cytochrome P450 inducers on 17alpha-ethinyloestradiol (EE2) conjugation by primary human hepatocytes. Br. J. Clin. Pharmacol. 1999a; 48(5)733–742
   PubMed Web of Science ®Google Scholar
• Li A. P., Lu C., Brent J. A., Pham C., Fackett A., Ruegg C. E., Silber P. M. Cryopreserved human hepatocytes: characterization of drug-metabolizing enzyme activities and applications in higher throughput screening assays for hepatotoxicity, metabolic stability, and drug-drug interaction potential. Chem. Biol. Interact. 1999b; 121(1)17–35
   PubMed Web of Science ®Google Scholar
• Li A. P. A review of the common properties of drugs with idiosyncratic hepatotoxicity and the “multiple determinant hypothesis” for the manifestation of idiosyncratic drug toxicity. Chem. Biol. Interact. 2002; 142(1–2)7–23
   PubMed Web of Science ®Google Scholar
• Li AP, Bode C., Sakai Y. A novel in vitro system, the integrated discrete multiple organ cell culture (IdMOC) system, for the evaluation of human drug toxicity: comparative cytotoxicity of tamoxifen towards normal human cells from five major organs and MCF-7 adenocarcinoma breast cancer cells. Chem. Biol. Interact. 2004; 150(1)129–136
   PubMed Web of Science ®Google Scholar
• Lieu Y. K., Hsu B. Y., Price W. A., Corkey B. E., Stanley C. A. Carnitine effects on coenzyme A profiles in rat liver with hypoglycin inhibition of multiple dehydrogenases. Am. J. Physiol. 1997; 272(3 Pt 1)E359–E366
   PubMed Web of Science ®Google Scholar
• Li A. P., Bode C., Sakai Y. A novel in vitro system, the integrated discrete multiple organ cell culture (IdMOC) system, for the evaluation of human drug toxicity: comparative cytotoxicity of tamoxifen towards normal human cells from five major organs and MCF-7 adenocarcinoma breast cancer cells. Chem. Biol. Interact. 2004; 150(1)129–136
   PubMed Web of Science ®Google Scholar
• Lin J. H., Lu A. Y. Inhibition and induction of cytochrome P450 and the clinical implications. Clin. Pharmacokinet 1998; 35(5)361–390
   PubMed Web of Science ®Google Scholar
• Liu X., LeCluyse E. L., Brouwer K. R., Gan L. S., Lemasters J. J., Stieger B., Meier P. J., Brouwer K. L. Biliary excretion in primary rat hepatocytes cultured in a collagen-sandwich configuration. Am. J. Physiol. 1999; 277(1 Pt 1)G12–21
   PubMed Web of Science ®Google Scholar
• Liu L., Pang K. S. The roles of transporters and enzymes in hepatic drug processing. Drug Metab. Dispos. 2005; 33(1)1–9
   PubMed Web of Science ®Google Scholar
• Loi C. M., Young M., Randinitis E., Vassos A., Koup J. R. Clinical pharmacokinetics of troglitazone. Pharmacokinet 1999a; 37(2)91–104
   PubMed Web of Science ®Google Scholar
• Loi C. M., Alvey C. W., Vassos A. B., Randinitis E. J., Sedman A. J., Koup J. R. Steady-state pharmacokinetics and dose proportionality of troglitazone and its metabolites. J. Clin. Pharmacol. 1999b; 39(9)920–926
   PubMed Web of Science ®Google Scholar
• Lu A. Y. H. Drug-metabolism research challenges in the new millennium: individual variability in drug therapy and drug safety. Drug Metab. Dispos. 1998; 26: 1217–1222
   PubMed Web of Science ®Google Scholar
• Lu C., Li A. P. Species comparison in P450 induction: effects of dexamethasone, omeprazole, and rifampin on P450 isoforms 1A and 3A in primary cultured hepatocytes from man, Sprague-Dawley rat, minipig, and beagle dog. Chem. Biol. Interact. 2001; 134(3)271–281
   PubMed Web of Science ®Google Scholar
• Lu Y., Cederbaum A. I. Cisplatin-induced hepatotoxicity is enhanced by elevated expression of cytochrome P450 2E1. Toxicol. Sci. 2006; 89(2)515–523
   PubMed Web of Science ®Google Scholar
• Madan A., Graham R. A., Carroll K. M., Mudra D. R., Burton L. A., Krueger L. A., Downey A. D., Czerwinski M., Forster J., Ribadeneira M. D., Gan L. S., LeCluyse E. L., Zech K., Robertson P., Jr., Koch P., Antonian L., Wagner G., Yu L., Parkinson A. Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab. Dispos. 2003; 31(4)421–431
   PubMed Web of Science ®Google Scholar
• Mankowski D. C., Laddison K. J., Christopherson P. A., Ekins S., Tweedie D. J., Lawton M. P. Molecular cloning, expression, and characterization of CYP2D17 from cynomolgus monkey liver. Arch. Biochem. Biophys. 1999; 372: 189–196
   PubMed Web of Science ®Google Scholar
• Masubuchi Y., Kano S., Horie T. Mitochondrial permeability transition as a potential determinant of hepatotoxicity of antidiabetic thiazolidinediones. Toxicology 2006; 222(3)233–9
   PubMed Web of Science ®Google Scholar
• Maurel P., Pichard L., Greuet J., Muntane J., Ourlin J. C., Duajat M. Inhibition and repression of CYP3A34 in primary cultures of human hepatocytes. Comparative analysis with clinical observations. Proceedings of the 10th International Symposium on Microsomes and Drug Oxidations, TorontoCanada, July, 18–21, 1994; 188–190
   Google Scholar
• Maurel P. The use of adult human hepatocytes in primary culture and other in vitro systems to investigate drug metabolism in man. Adv. Drug Del. Rev. 1996; 22: 105–132
   Web of Science ®Google Scholar
• McDonagh A. F., Palma L. A., Lauff J. J., Wu T. W. Origin of mammalian biliprotein and rearrangement of bilirubin glucuronides in vivo in the rat. J. Clin. Invest. 1984; 74(3)763–770
   PubMed Web of Science ®Google Scholar
• McDonnell W. M., Scheiman J. M., Traber P. G. Induction of cytochrome P450IA genes (CYP1A) by omeprazole in the human alimentary tract. Gastroenterology 1992; 103(5)1509–1516
   PubMed Web of Science ®Google Scholar
• McGinnity D. F., Soars M. G., Urbanowicz R. A., Riley R. J. Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance. Drug Metab. Dispos. 2004; 32: 1247–1253
   PubMed Web of Science ®Google Scholar
• McInnes G. T., Brodie M. J. Drug interactions that matter. A critical reappraisal. Drugs 1998; 36(1)83–110
   Web of Science ®Google Scholar
• Meijer D. K., van Montfoort J. E. Interactions of cationic drugs and cardiac glycosides at the hepatic uptake level: studies in the rat in vivo, isolated perfused rat liver, isolated rat hepatocytes and oocytes expressing oatp2. Arch. Pharm. Res. 2002; 25(4)397–415
   PubMed Web of Science ®Google Scholar
• Meunier V., Bourrie M., Julian B., Marti E., Guillou F., Berger Y., Fabre G. Expression and induction of CYP1A1/1A2, CYP2A6 and CYP3A4 in primary cultures of human hepatocytes: a 10-year follow-up. Xenobiotica 2000; 30(6)589–607
   PubMed Web of Science ®Google Scholar
• Moore L. B., Parks D. J., Jones S. A., Bledsoe R. K., Consler T. G., Stimmel J. B., Goodwin B., Liddle C., Blanchard S. G., Willson T. M., Collins J. L., Kliewer S. A. Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J. Biol. Chem. 2000; 275(20)15122–15127
   PubMed Web of Science ®Google Scholar
• Moshage H. J., Rijntjes P. J., Hafkenscheid J. C., Roelofs H. M., Yap S. H. Primary culture of cryopreserved adult human hepatocytes on homologous extracellular matrix and the influence of monocytic products on albumin synthesis. J. Hepatol. 1988; 7(1)34–44
   PubMed Web of Science ®Google Scholar
• Musat A. I., Sattler C., Sattler G. L., Pitot H. C. Re-establishment of cell polarity of hepatocytes in primary culture. Hepatology 1993; 18: 198–205
   PubMed Web of Science ®Google Scholar
• Nagar S., Remmel R. P. Uridine diphosphoglucuronosyltransferase pharmacogenetics and cancer. Oncogene 2006; 25(11)1659–1672
   PubMed Web of Science ®Google Scholar
• Narayanan P. K., Hart T., Elcock F., Zhang C., Hahn L., McFarland D., Schwartz L., Morgan D. G., Bugelski P. Troglitazone-induced intracellular oxidative stress in rat hepatoma cells: a flow cytometric assessment. Cytometry A. 2003; 52(1)28–35
   PubMed Web of Science ®Google Scholar
• Naritomi Y., Terashita S., Kagayama A., Sugiyama Y. Utility of hepatocytes in predicting drug metabolism: comparison of hepatic intrinsic clearance in rats and humans in vivo and in vitro. Drug Metab. Dispos. 2003; 31(5)580–588
   PubMed Web of Science ®Google Scholar
• Nelson D. R., Kamataki T., Waxman D. J., Guengerich F. P., Estabrook R. W., Feyereisen R., Gonzalez F. J., Coon M. J., Gunsalus I. C., Gotoh O., et al. The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell. Biol. 1993; 12(1)1–51
   PubMed Web of Science ®Google Scholar
• Neuschwander-Tetri B. A., Isley W. L., Oki J. C., Ramrakhiani S., Quiason S. G., Phillips N. J., Brunt E. M. Troglitazone-induced hepatic failure leading to liver transplantation. A case report. Ann. Intern. Med. 1998; 129(1)38–41
   PubMed Web of Science ®Google Scholar
• Nishizato Y., Ieiri I., Suzuki H., Kimura M., Kawabata K., Hirota T., Takane H., Irie S., Kusuhara H., Urasaki Y., Urae A., Higuchi S., Otsubo K., Sugiyama Y. Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Clin. Pharmacol. Ther. 2003; 73(6)554–565
   PubMed Web of Science ®Google Scholar
• Nomeir A. A., Ruegg C., Shoemaker M., Favreau L. V., Palamanda J. R., Silber P., Lin C. C. Inhibition of CYP3A4 in a rapid microtiter plate assay using recombinant enzyme and in human liver microsomes using conventional substrates. Drug Metab. Dispos. 2001; 29(5)748–753
   PubMed Web of Science ®Google Scholar
• Noureddin B. N., Seoud M., Bashur Z., Shamseddin A., Khalil A. Ocular toxicity in low-dose tamoxifen: a prospective study. Eye. 1999; 13: 729–733
   PubMed Web of Science ®Google Scholar
• Novak R. F., Woodcroft K. J. The alcohol-inducible form of cytochrome P450 (CYP 2E1): role in toxicology and regulation of expression. Arch. Pharm. Res. 2000; 23(4)267–282
   PubMed Web of Science ®Google Scholar
• Nozawa T., Sugiura S., Nakajima M., Goto A., Yokoi T., Nezu J., Tsuji A., Tamai I. Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug Metab. Dispos. 2004; 32(3)291–294
   PubMed Web of Science ®Google Scholar
• Nussler A., Konig S., Ott M., Sokal E., Christ B., Thasler W., Brulport M., Gabelein G., Schormann W., Schulze M., Ellis E., Kraemer M., Nocken F., Fleig W., Manns M., Strom S. C., Hengstler J. G. Present status and perspectives of cell-based therapies for liver diseases. J. Hepatol. 2006; 200: 6, Apr 27; [Epub ahead of print]
   Google Scholar
• Obach R. S. Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metab. Dispos. 1999; 27(11)1350–1359
   PubMed Web of Science ®Google Scholar
• O'Brien P. J., Chan K., Silber P. M. Human and animal hepatocytes in vitro with extrapolation in vivo. Chem. Biol. Interact. 2004; 150: 97–114
   PubMed Web of Science ®Google Scholar
• O'Brien P. J., Siraki A. G. Accelerated cytotoxicity mechanism screening using drug metabolising enzyme modulators. Curr. Drug Metab. 2005; 6(2)101–109
   PubMed Web of Science ®Google Scholar
• O'Donohoe A., O'Flynn K., Shields K., Hawi Z., Gill M. MDMA toxicity: no evidence for a major influence of metabolic genotype at CYP2D6. Addict. Biol. 1998; 3: 309–314
   PubMed Web of Science ®Google Scholar
• Ohno M., Yamaguchi I., Ito T., Saiki K., Yamamoto I., Azuma J. Circadian variation of the urinary 6beta-hydroxycortisol to cortisol ratio that would reflect hepatic CYP3A activity. Eur. J. Clin. Pharmacol. 2000; 55(11–12)861–865
   PubMed Web of Science ®Google Scholar
• Olinga P., Merema M., Hof I. H., de Jong K. P., Slooff M. J., Meijer D. K., Groothuis G. M. Effect of human liver source on the functionality of isolated hepatocytes and liver slices. Drug Metab. Dispos. 1998a; 26(1)5–11
   PubMed Web of Science ®Google Scholar
• Olinga P., Merema M., Hof I. H., Slooff M. J., Proost J. H., Meijer D. K., Groothuis G. M. Characterization of the uptake of rocuronium and digoxin in human hepatocytes: carrier specificity and comparison with in vivo data. J. Pharmacol. Exp. Ther. 1998b; 285(2)506–510
   PubMed Web of Science ®Google Scholar
• Olinga P., Hof I. H., Merema M. T., Smit M., de Jager M. H., Swart P. J., Slooff M. J., Meijer D. K., Groothuis G. M. The applicability of rat and human liver slices to the study of mechanisms of hepatic drug uptake. J. Pharmacol. Toxicol. Methods 2001; 45(1)55–63
   PubMed Web of Science ®Google Scholar
• Ostapowicz G., Fontana R. J., Schiodt F. V., Larson A., Davern T. J., Han S. H., McCashland T. M., Shakil A. O., Hay J. E, Hynan L, Crippin J. S., Blei A. T., Samuel G., Reisch J., Lee W. M. U.S. Acute Liver Failure Study Group. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann. Intern. Med. 2002; 137(12)947–954
   PubMed Web of Science ®Google Scholar
• Park B. K., Kitteringham N. R., Maggs J. L., Pirmohamed M., Williams D. P. The role of metabolic activation in drug-induced hepatotoxicity. Annu. Rev. Pharmacol. Toxicol. 2005; 45: 177–202
   PubMed Web of Science ®Google Scholar
• Parker A. J., Houston J. B. Rate limiting steps in hepatic drug clearance: comparison of hepatocellular uptake and metabolism with microsomal metabolism for three HIV protease inhibitors. 2006, Submitted for publication
   Google Scholar
• Parkinson A. Biotransformation of xenobiotics. Casserett and Doull's Toxicology. The Basic Science of Poisons 6th, C. D. Klassen. McGraw-Hill, New York 2001; 133–224, Chapter 6.
   Google Scholar
• Parkinson A., Mudra D. R., Johnson C., Dwyer A., Carroll K. M. The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes. Toxicol. Appl. Pharmacol. 2004; 199(3)193–209
   PubMed Web of Science ®Google Scholar
• Pascussi J. M., Drocourt L., Fabre J. M., Maurel P., Vilarem M. J. Dexamethasone induces pregnane X receptor and retinoid X receptor-alpha expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane X receptor activators. Mol. Pharmacol. 2000a; 58(2)361–372
   PubMed Web of Science ®Google Scholar
• Pascussi J. M., Gerbal-Chaloin S., Fabre J. M., Maurel P., Vilarem M. J. Dexamethasone enhances constitutive androstane receptor expression in human hepatocytes: consequences on cytochrome P450 gene regulation. Mol. Pharmacol. 2000b; 58(6)1441–1450
   PubMed Web of Science ®Google Scholar
• Pascussi J. M., Drocourt L., Gerbal-Chaloin S., Fabre J. M., Maurel P., Vilarem M. J. Dual effect of dexamethasone on CYP3A4 gene expression in human hepatocytes. Sequential role of glucocorticoid receptor and pregnane X receptor. Eur. J. Biochem. 2001; 268(24)6346–6358
   PubMedGoogle Scholar
• Pascussi J. M., Gerbal-Chaloin S., Drocourt L., Maurel P., Vilarem M. J. The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. Biochim. Biophys. Acta. 2003; 1619(3)243–253
   PubMed Web of Science ®Google Scholar
• Paulson S. K., Engel L., Reitz B., Bolten S., Burton E. G., Maziasz T. J., Yan B., Schoenhard G. L. Evidence for polymorphism in the canine metabolism of the cyclooxygenase 2 inhibitor, celecoxib. Drug Metab. Dispos. 1999; 27(10)1133–1142
   PubMed Web of Science ®Google Scholar
• Peters T. S. Do preclinical testing strategies help predict human hepatotoxic potentials?. Toxicol. Pathol. 2005; 33(1)146–154
   PubMed Web of Science ®Google Scholar
• Pichard-Garcia L., Hyland R., Baulieu J., Fabre J. M., Milton A., Maurel P. Human hepatocytes in primary culture predict lack of cytochrome P-450 3A4 induction by eletriptan in vivo. Drug Metab. Dispos. 2000; 28(1)51–57
   PubMed Web of Science ®Google Scholar
• Pichard-Garcia L., Gerbal-Chaloin S., Ferrini J. B., Fabre J. M., Maurel P. Use of long-term cultures of human hepatocytes to study cytochrome P450 gene expression. Methods Enzymol. 2002; 357: 311–321
   PubMed Web of Science ®Google Scholar
• Ponsoda X., Pareja E., Gómez-Lechón M. J., Fabra R., Carrasco E., Trulllenque R., Castell J. V. Drug biotransformation by human hepatocytes: in vitro/in vivo metabolism by cells from the same donor. J. Hepatol. 2001; 33: 19–25
   Web of Science ®Google Scholar
• Posti K., Leinonen S., Tetri S., Kottari S., Viitala P., Pelkonen O., Raunio H. Modulation of murine phenobarbital-inducible CYP2A5, CYP2B10 and CYP1A enzymes by inhibitors of protein kinases and phosphatases. Eur. J. Biochem. 1999; 264(1)19–26
   PubMedGoogle Scholar
• Prabhu S., Fackett A., Lloyd S., McClellan H. A., Terrell C. M., Silber P. M., Li A. P. Identification of glutathione conjugates of troglitazone in human hepatocytes. Chem. Biol. Interact. 2002; 142(1–2)83–97
   PubMed Web of Science ®Google Scholar
• Prueksaritanont T., Richards K. M., Qiu Y., Strong-Basalyga K., Miller A., Li C., Eisenhandler R., Carlini E. J. Comparative effects of fibrates on drug metabolizing enzymes in human hepatocytes. Pharm. Res. 2005; 22(1)71–78
   PubMed Web of Science ®Google Scholar
• Raucy J. L., Lasker J., Ozaki K., Zoleta V. Regulation of CYP2E1 by ethanol and palmitic acid and CYP4A11 by clofibrate in primary cultures of human hepatocytes. Toxicol. Sci. 2004; 79(2)233–241
   PubMed Web of Science ®Google Scholar
• Reichard J. F., Doorn J. A., Simon F., Taylor M. S., Petersen D. R. Characterization of multidrug resistance-associated protein 2 in the hepatocellular disposition of 4-hydroxynonenal. Arch. Biochem. Biophys. 2003; 411(2)243–250
   PubMed Web of Science ®Google Scholar
• Rialland L., Guyomard C., Scotte M., Chesne C., Guillouzo A. Viability and drug metabolism capacity of alginate-entrapped hepatocytes after cryopreservation. Cell Biol. Tox. 2000; 16: 105–116
   PubMed Web of Science ®Google Scholar
• Richert L., Binda D., Hamilton G., Viollon-Abadie C., Alexandre E., Bigot-Lasserre D., Bars R., Coassolo P., LeCluyse E. Evaluation of the effect of culture configuration on morphology, survival time, antioxidant status and metabolic capacities of cultured rat hepatocytes. Toxicol. in Vitro. 2002; 16(1)89–99
   PubMed Web of Science ®Google Scholar
• Richert L., Alexandre E., Lloyd T., Orr S., Viollon-Abadie C., Patel R., Kingston S., Berry D., Dennison A., Heyd B., Mantion G., Jaeck D. Tissue collection, transport and isolation procedures required to optimize human hepatocyte isolation from waste liver surgical resections. A multilaboratory study. Liver Int. 2004; 24(4)371–378
   PubMed Web of Science ®Google Scholar
• Richert L., Liguori M. J., Abadie C., Heyd B., Mantion G., Halkic N., Waring J. F. Gene expression in human hepatocytes in suspension after isolation is similar to the liver of origin, is not affected by hepatocyte cold storage and cryopreservation, but is strongly changed after hepatocyte plating. Drug Metab. Dispos. 2006; 34(5)870–879
   PubMed Web of Science ®Google Scholar
• Ring B. J., Patterson B. E., Mitchell M. I., Vandenbranden M., Gillespie J., Bedding A. W., Jewell H., Payne C. D., Forgue S. T., Eckstein J., Wrighton S. A., Phillips D. L. Effect of tadalafil on cytochrome P450 3A4-mediated clearance: studies in vitro and in vivo. Clin. Pharmacol. Ther. 2005; 77(1)63–75
   PubMed Web of Science ®Google Scholar
• Ringel M., Oesch F., Gerl M., Klebach M., Quint M., Bottger T., Hengstler J. G. Permissive and suppressive effects of dexamethasone on enzyme induction in hepatocyte co-cultures. Xenobiotica 2002; 32(8)653–666
   PubMed Web of Science ®Google Scholar
• Ringel M., von Mach M. A., Santos R., Feilen P. J., Brulport M., Hermes M., Bauer A. W., Schormann W., Tanner B., Schon M. R., Oesch F., Hengstler J. G. Hepatocytes cultured in alginate microspheres: an optimized technique to study enzyme induction. Toxicology 2005; 206(1)153–167
   PubMed Web of Science ®Google Scholar
• Robertson P., DeCory H. H., Madan A., Parkinson A. In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab. Dispos. 2000; 28(6)664–671
   PubMed Web of Science ®Google Scholar
• Rodriguez-Antona C., Donato M. T., Gómez-Lechón M. J., Castell J. V. CYP mRNA expression in human liver and its relationship with enzyme activity. Arch. Biochem. Biophys. 2001; 15: 308–315
   Web of Science ®Google Scholar
• Rodríguez-Antona C., Donato M. T., Boobis A., Edwards R. J., Watts P. S., Castell J. V., Gómez-Lechón M. J. Cytochrome P-450 expression in human hepatocytes and human hepatoma cell lines. Molecular mechanisms that determine the lower expression in cultured cells. Xenobiotica 2002; 32: 505–520
   PubMed Web of Science ®Google Scholar
• Rose K. A., Kostrubsky V., Sahi J. Hepatobiliary disposition in primary cultures of dog and monkey hepatocytes. Mol. Pharm. 2006; 3(3)266–274
   PubMed Web of Science ®Google Scholar
• Roussel F., Duignan D. B., Lawton M. P., Obach R. S., Strick C. A., Tweedie D. J. Expression and characterization of canine cytochrome P450 2D15. Arch. Biochem. Biophys. 1998; 357: 27–36
   PubMed Web of Science ®Google Scholar
• Roymans D., Van Looveren C., Leone A., Parker J. B., McMillian M., Johnson M. D., Koganti A., Gilissen R., Silber P., Mannens G., Meuldermans W. Determination of cytochrome P450 1A2 and cytochrome P450 3A4 induction in cryopreserved human hepatocytes. Biochem. Pharmacol. 2004; 67(3)427–437
   PubMed Web of Science ®Google Scholar
• Roymans D., Annaert P., Van Houdt J., Weygers A., Noukens J., Sensenhauser C., Silva J., Van Looveren C., Hendrickx J., Mannens G., Meuldermans W. Expression and induction potential of cytochromes P450 in human cryopreserved hepatocytes. Drug Metab. Dispos. 2005; 33(7)1004–1016
   PubMed Web of Science ®Google Scholar
• Ruegg C. E., Silber P. M., Mughal R. A., Ismail J., Lu C., Bode D. C., Li A. P. Cytochrome-P450 induction and comjugated metabolism in primary human hepatocytes after cryopreservation. In Vitro Technol. 1997; 10: 217–222
   Web of Science ®Google Scholar
• Ruepp S. U., Tonge R. P., Shaw J., Wallis N., Pognan F. Genomics and proteomics analysis of acetaminophen toxicity in mouse liver. Toxicol. Sci. 2002; 65(1)135–150
   PubMed Web of Science ®Google Scholar
• Ruhnke M., Nussler A. K., Ungefroren H., Hengstler J. G., Kremer B., Hoeckh W., Gottwald T., Heeckt P., Fandrich F. Human monocyte-derived neohepatocytes: a promising alternative to primary human hepatocytes for autologous cell therapy. Transplantation 2005a; 79: 1097–1103
   PubMed Web of Science ®Google Scholar
• Ruhnke M., Ungefroren H., Nussler A., Martin F., Brulport M., Schormann W., Hengstler J. G., Klapper W., Ulrichs K., Hutchinson J. A., Soria B., Parwaresch R. M., Heeckt P., Kremer B., Fändrich F. Reprogramming of Human Peripheral Blood Monocytes into Functional Hepatocyte and Pancreatic Islet-like Cells. Gastroenterology 2005b, In press
   PubMed Web of Science ®Google Scholar
• Ruiz M. L., Villanueva S. S., Luquita M. G., Vore M., Mottino A. D., Catania V. A. Ethynylestradiol increases expression and activity of rat liver MRP3. Drug Metab. Dispos. 2006; 34(6)1030–1034
   PubMed Web of Science ®Google Scholar
• Runge D., Runge D. M., Jager D., Lubecki K. A., Beer Stolz D., Karathanasis S., Kietzmann T., Strom S. C., Jungermann K., Fleig W. E., Michalopoulos G. K. Serum-free, long-term cultures of human hepatocytes: maintenance of cell morphology, transcription factors, and liver-specific functions. Biochem. Biophys. Res. Commun. 2000; 269(1)46–53
   PubMed Web of Science ®Google Scholar
• Sahi J., Milad M. A., Zheng X., Rose K. A., Wang H., Stilgenbauer L., Gilbert D., Jolley S., Stern R. H., LeCluyse E. L. Avasimibe induces CYP3A4 and multiple drug resistance protein 1 gene expression through activation of the pregnane X receptor. J. Pharmacol. Exp. Ther. 2003; 306(3)1027–1034
   PubMed Web of Science ®Google Scholar
• Sahi J. Use of in vitro transporter assays to understand hepatic and renal disposition of new drug candidates. Expert Opin. Drug Metab. Toxicol. 2005; 1(3)409–427
   PubMedGoogle Scholar
• Salonen J. S., Nyman L., Boobis A. R., Edwards R. J., Watts P., Lake B. G., Price R. J., Renwick A. B., Gomez-Lechon M. J., Castell J. V., Ingelman-Sundberg M., Hidestrand M., Guillouzo A., Corcos L., Goldfarb P. S., Lewis D. F., Taavitsainen P., Pelkonen O. Comparative studies on the cytochrome p450-associated metabolism and interaction potential of selegiline between human liver-derived in vitro systems. Drug Metab. Dispos. 2003; 31(9)1093–1102
   PubMed Web of Science ®Google Scholar
• Sandker G. W., Weert B., Olinga P., Wolters H., Slooff M. J., Meijer D. K., Groothuis G. M. Characterization of transport in isolated human hepatocytes. A study with the bile acid taurocholic acid, the uncharged ouabain and the organic cations vecuronium and rocuronium. Biochem. Pharmacol. 1994; 47(12)2193–2200
   PubMed Web of Science ®Google Scholar
• Scala S., Akhmed N., Rao U. S., Paull K., Lan L. B., Dickstein B., Lee J. S., Elgemeie G. H., Stein W. D., Bates S. E. P-glycoprotein substrates and antagonists cluster into two distinct groups. Mol. Pharmacol. 1997; 51(6)1024–1033
   PubMed Web of Science ®Google Scholar
• Schuppe-Koistinen I., Frisk A. L., Janzon L. Molecular profiling of hepatotoxicity induced by a aminoguanidine carboxylate in the rat: gene expression profiling. Toxicology 2002; 179: 197–219
   PubMed Web of Science ®Google Scholar
• Schuster D., Laggner C., Langer T. Why drugs fail—a study on side effects in new chemical entities. Curr. Pharm. Des. 2005; 11: 3545–3590
   PubMed Web of Science ®Google Scholar
• Schwartz R. E., Reyes M., Koodie L., Jiang Y., Blackstad M., Lund T., Lenvik T., Johnson S., Hu W. S., Verfaillie C. M. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J. Clin. Invest. 2002; 109: 1291–1302
   PubMed Web of Science ®Google Scholar
• Seitz S., Kretz-Rommel A., Oude Elferink R. P., Boelsterli U. A. Selective protein adduct formation of diclofenac glucuronide is critically dependent on the rat canalicular conjugate export pump (MRP2). Chem. Res. Toxicol. 1998; 11(5)513–519
   PubMed Web of Science ®Google Scholar
• Shah R. R. Mechanistic basis of adverse drug reactions: the perils of inappropriate dose schedules. Expert. Opin. Drug. Saf. 2005; 4: 103–128
   PubMedGoogle Scholar
• Shibata Y., Takahashi H., Chiba M., Ishii Y. Prediction of hepatic clearance and availability by cryopreserved human hepatocytes: an application of serum incubation method. Drug Metab. Dispos. 2002; 30: 892–896
   PubMed Web of Science ®Google Scholar
• Shimada T., Yamazaki H., Mimura M., Inui Y., Guengerich F. P. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther. 1994; 270(1)414–423
   PubMed Web of Science ®Google Scholar
• Shishido S., Koga H., Harada M., Kumemura H., Hanada S., Taniguchi E., Kumashiro R., Ohira H., Sato Y., Namba M., Ueno T., Sata M. Hydrogen peroxide overproduction in megamitochondria of troglitazone-treated human hepatocytes. Hepatology 2003; 37(1)136–147
   PubMed Web of Science ®Google Scholar
• Shitara Y., Sugiyama D., Kusuhara H., Kato Y., Abe T., Meier P. J., Itoh T., Sugiyama Y. Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm. Res. 2002; 19(2)147–153
   PubMed Web of Science ®Google Scholar
• Shitara Y., Itoh T., Satoh H., Li A. P., Sugiyama Y. Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. J. Pharmacol. Exp. Ther. 2003; 304: 610–616
   PubMed Web of Science ®Google Scholar
• Shitara Y Horie T, Sugiyama Y. Transporters as a determinant of drug clearance and tissue distribution. Eur. J. Pharm. Sci. 2006; 27(5)425–446
   PubMed Web of Science ®Google Scholar
• Shou M., Norcross R., Sandig G., Lu P., Li Y., Lin Y., Mei Q., Rodrigues A. D., Rushmore T. H. Substrate specificity and kinetic properties of seven heterologously expressed dog cytochromes p450. Drug Metab. Dispos. 2003; 31: 1161–1169
   PubMed Web of Science ®Google Scholar
• Sidenius U., Skonberg C., Olsen J., Hansen S. H. In vitro reactivity of carboxylic acid-CoA thioesters with glutathione. Chem. Res. Toxicol. 2004; 17(1)75–81
   PubMed Web of Science ®Google Scholar
• Sidhu J. S., Farin F. M., Omiecinski C. J. Influence of extracellular matrix overlay on phenobarbital-mediated induction of CYP2B1, 2B2, and 3A1 genes in primary adult rat hepatocyte culture. Arch. Biochem. Biophys. 1993; 301(1)103–113
   PubMed Web of Science ®Google Scholar
• Sidhu J. S., Omiecinski C. J. Modulation of xenobiotic-inducible cytochrome P450 gene expression by dexamethasone in primary rat hepatocytes. Pharmacogenetics 1995; 5(1)24–36
   PubMedGoogle Scholar
• Sidhu J. S., Liu F., Omiecinski C. J. Phenobarbital responsiveness as a uniquely sensitive indicator of hepatocyte differentiation status: requirement of dexamethasone and extracellular matrix in establishing the functional integrity of cultured primary rat hepatocytes. Exp. Cell Res. 2004; 292(2)252–264
   PubMed Web of Science ®Google Scholar
• Silva J. M., Day S. H., Nicoll-Griffith D. A. Induction of cytochrome-P450 in cryopreserved rat and human hepatocytes. Chem. Biol. Interact. 1999; 121(1)49–63
   PubMed Web of Science ®Google Scholar
• Silva M. F. B., Ruiter J. P. N., Ijlst L., Allers P., ten Brink H. J., Jakobs C., Duran M., de Almedia I. T., Wander R. J. A. Synthesis and intramitochondrial levels of valproyl-coenzyme A metabolites. Analyt. Biochem. 2001; 290(1)60–67
   PubMed Web of Science ®Google Scholar
• Silva M. F., Ijlst L., Allers P., Jakobs C., Duran M., de Almeida I. T., Wanders R. J. Valproyl-dephosphoCoA: a novel metabolite of valproate formed in vitro in rat liver mitochondria. Drug Metab. Dispos. 2004; 32(11)1304–1310
   PubMed Web of Science ®Google Scholar
• Singh S. S. Preclinical pharmacokinetics: an approach towards safer and efficacious drugs. Curr. Drug Metab. 2006; 7: 165–182
   PubMed Web of Science ®Google Scholar
• Skett P., Roberts P., Khan S. Maintenance of steroid metabolism and hormone responsiveness in cryopreserved dog, monkey and human hepatocytes. Chem. Biol. Interact. 1999; 121(1)65–76
   PubMed Web of Science ®Google Scholar
• Smirlis D., Muangmoonchai R., Edwards M., Phillips I. R., Shephard E. A. Orphan receptor promiscuity in the induction of cytochromes p450 by xenobiotics. J. Biol. Chem. 2001; 276(16)12822–12826
   PubMed Web of Science ®Google Scholar
• Smith P. C., McDonagh A. F., Benet L. Z. Irreversible binding of zomepirac to plasma protein in vitro and in vivo. J. Clin. Invest. 1986; 77(3)934–939
   PubMed Web of Science ®Google Scholar
• Smith D. A., Abel S. M., Hyland R., Jones B. C. Human cytochrome P450s: selectivity and measurement in vivo. Xenobiotica 1998; 28: 1095–1128
   PubMed Web of Science ®Google Scholar
• Smith D. A. Induction and drug development. Eur. J. Pharm. Sci. 2000; 11(3)185–189
   PubMed Web of Science ®Google Scholar
• Soars M. G., Burchell B., Riley R. J. In vitro analysis of human drug glucuronidation and prediction of in vivo metabolic clearance. J. Pharm. Exp. Ther. 2002; 301: 382–390
   PubMed Web of Science ®Google Scholar
• Soars M. G., Petullo D. M., Eckstein J. A., Kasper S. C., Wrighton S. A. An assessment of udp-glucuronosyltransferase induction using primary human hepatocytes. Drug Metab. Dispos. 2004; 32(1)140–148
   PubMed Web of Science ®Google Scholar
• Squires E. J., Sueyoshi T., Negishi M. Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver. J. Biol. Chem. 2004; 279(47)49307–49314
   PubMed Web of Science ®Google Scholar
• Stieger B., Fattinger K., Madon J., Kullak-Ublick G. A., Meier P. J. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (BSEP) of rat liver. Gastroenterology 2000; 118(2)422–430
   PubMed Web of Science ®Google Scholar
• Stogniew M., Fenselau C. Electrophilic reactions of acyl-linked glucuronides. Formation of clofibrate mercapturate in humans. Drug Metab. Dispos. 1982; 10(6)609–613
   PubMed Web of Science ®Google Scholar
• Stresser D. M., Kupfer D. Monospecific antipeptide antibody to cytochrome P-450 2B6. Drug Metab. Dispos. 1999; 27(4)517–525
   PubMed Web of Science ®Google Scholar
• Su T., Waxman D. J. Impact of dimethyl-sulfoxide on expression of nuclear receptors and drug-inducible cytochromes P450 in primary rat hepatocytes. Arch. Biochem. Biophys. 2004; 424(2)226–234
   PubMed Web of Science ®Google Scholar
• Sueyoshi T., Kawamoto T., Zelko I., Honkakoski P., Negishi M. The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. J. Biol. Chem. 1999; 274(10)6043–6046
   PubMed Web of Science ®Google Scholar
• Szabo K., Bakos E., Welker E., Muller M., Goodfellow H. R., Higgins C. F., Varadi A., Sarkadi B. Phosphorylation site mutations in the human multidrug transporter modulate its drug-stimulated ATPase activity. J. Biol. Chem. 1997; 272(37)23165–23171
   PubMed Web of Science ®Google Scholar
• Tang W., Borel A. G., Fujimiya T., Abbott F. S. Fluorinated Analogs As Mechanistic Probes in Valproic Acid Hepatotoxicity—Hepatic Microvesicular Steatosis and Glutathione Status. Chem. Res. Toxicol. 1995; 8(5)671–682
   PubMed Web of Science ®Google Scholar
• Tang C., Lin J. H., Lu A. Y. Metabolism-based drug-drug interactions: what determines individual variability in cytochrome P450 induction?. Drug Metab. Dispos. 2005; 33(5)603–613
   PubMed Web of Science ®Google Scholar
• Terry T. L., Gallin W. J. Effects of fetal calf serum and disruption of cadherin function on the formation of bile canaliculi between hepatocytes. Exp. Cell Res. 1994; 214: 642–653
   PubMed Web of Science ®Google Scholar
• Terry C., Mitry R. R., Lehec S. C., Muiesan P., Rela M., Heaton N. D., Hughes R. D., Dhawan A. The effects of cryopreservation on human hepatocytes obtained from different sources of liver tissue. Cell Transplant 2005; 14(8)585–594
   PubMed Web of Science ®Google Scholar
• Terry C., Dhawan A., Mitry R. R., Lehec S. C., Hughes R. D. Preincubation of rat and human hepatocytes with cytoprotectants prior to cryopreservation can improve viability and function upon thawing. Liver Transplant 2006; 12(1)165–177
   PubMed Web of Science ®Google Scholar
• Tirmenstein M. A., Hu C. X., Gales T. L., Maleeff B. E., Narayanan P. K., Kurali E., Hart T. K., Thomas H. C., Schwartz L. W. Effects of troglitazone on HepG2 viability and mitochondrial function. Toxicol. Sci. 2002; 69(1)131–138
   PubMed Web of Science ®Google Scholar
• Tirona R. G., Leake B. F., Merino G., Kim R. B. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J. Biol. Chem. 2001; 276(38)35669–35675
   PubMed Web of Science ®Google Scholar
• Treiber A., Schneiter R., Delahaye S., Clozel M. Inhibition of organic anion transporting polypeptide-mediated hepatic uptake is the major determinant in the pharmacokinetic interaction between bosentan and cyclosporin A in the rat. J. Pharmacol. Exp. Ther. 2004; 308(3)1121–1129
   PubMed Web of Science ®Google Scholar
• Turncliff R. Z., Meier P. J., Brouwer K. L. Effect of dexamethasone treatment on the expression and function of transport proteins in sandwich-cultured rat hepatocytes. Drug Metab. Dispos. 2004; 32(8)834–849
   PubMed Web of Science ®Google Scholar
• Tuschl G., Mueller S. O. Effects of cell culture conditions on primary rat hepatocytes-cell morphology and differential gene expression. Toxicology 2006; 218(2–3)205–215
   PubMed Web of Science ®Google Scholar
• Uwai Y., Saito H., Inui K. Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter. Eur J. Pharmacol. 2000; 409(1)31–36
   PubMed Web of Science ®Google Scholar
• van Breemen R. B., Fenselau C. Acylation of albumin by 1-O-acyl glucuronides. Drug Metab. Dispos. 1985; 13(3)318–320
   PubMed Web of Science ®Google Scholar
• von Mach M. A., Hengstler J. G., Brulport M., Eberhardt M., Schormann W., Hermes M., Prawitt D., Zabel B., Grosche J., Reichenbach A., Muller B., Weilemann L. S., Zulewski H. In vitro cultured islet-derived progenitor cells of human origin express human albumin in severe combined immunodeficiency mouse liver in vivo. Stem Cells. 2004; 22: 1134–41
   PubMed Web of Science ®Google Scholar
• van Montfoort J. E., Hagenbuch B., Groothuis G. M. M., Koepsell H., Meier P. J., Meijer D. K. F. Drug uptake systems in liver and kidney. Curr. Drug Metab. 2003; 4: 185–211
   PubMed Web of Science ®Google Scholar
• Wahlstrom A., Persson K., Rane A. Metabolic interaction between morphine and naloxone in human liver. A common pathway of glucuronidation?. Drug Metab. Dispos. 1989; 17: 218–220
   PubMed Web of Science ®Google Scholar
• Walgren J. L., Mitchell M. D., Thompson D. C. Role of metabolism in drug-induced idiosyncratic hepatotoxicity. Crit. Rev. Toxicol. 2005; 35(4)325–331
   PubMed Web of Science ®Google Scholar
• Wang Y., Ripperger J., Fey G. H., Samols D., Kordula T., Wetzler M., Van Etten R. A., Baumann H. Modulation of hepatic acute phase gene expression by epidermal growth factor and Src protein tyrosine kinases in murine and human hepatic cells. Hepatology 1999; 30(3)682–697
   PubMed Web of Science ®Google Scholar
• Wang H., Faucette S. R., Gilbert D., Jolley S. L., Sueyoshi T., Negishi M., LeCluyse E. L. Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes. Drug Metab. Dispos. 2003; 31(5)620–630
   PubMed Web of Science ®Google Scholar
• Waring J. F., Ciurlionis R., Jolly R. A., Heindel M, Ulrich R. G. Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity. Toxicol. Lett. 2001; 120: 359–368
   PubMed Web of Science ®Google Scholar
• Waxman D. J. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch. Biochem. Biophys. 1999; 369(1)11–23
   PubMed Web of Science ®Google Scholar
• Wenz A., Thorpe C., Ghisla S. Inactivation of general acyl-CoA dehydrogenase from pig kidney by a metabolite of hypoglycin A. J. Biol. Chem. 1981; 256(19)9809–9812
   PubMed Web of Science ®Google Scholar
• Waxman D. J., Pampori N. A., Ram P. A., Agrawal A. K., Shapiro B. H. Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450. Proc. Natl. Acad. Sci. USA 1991a; 88(15)6868–6872
   PubMed Web of Science ®Google Scholar
• Waxman D. J., Lapenson D. P., Aoyama T., Gelboin H. V., Gonzalez F. J., Korzekwa K. Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s. Arch. Biochem. Biophys. 1991b; 290(1)160–166
   PubMed Web of Science ®Google Scholar
• Wenz A., Thorpe C., Ghisla S. Inactivation of general acyl-CoA dehydrogenase from pig kidney by a metabolite of hypoglycin A. J. Biol. Chem. 1981; 256(19)9809–9812
   PubMed Web of Science ®Google Scholar
• Williams G. M., Bermudez E., Scaramuzzino D. Rat hepatocyte primary cell cultures. III. Improved dissociation and attachment techniques and the enhancement of survival by culture medium. In Vitro. 1977; 13: 809–817
   PubMedGoogle Scholar
• Wilson Z. E., Rostami-Hodjegan A., Burn J. L., Tooley A., Boyle J., Ellis S. W., Tucker G. T. Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver. Br. J. Clin. Pharmacol. 2003; 56(4)433–440
   PubMed Web of Science ®Google Scholar
• Witherow L. E., Houston J. B. Sigmoidal kinetics of CYP3A substrates: an approach for scaling dextromethorphan metabolism in hepatic microsomes and isolated hepatocytes to predict in vivo clearance in rat. J. Pharmacol. Exp. 1999; 290: 58–65
   PubMed Web of Science ®Google Scholar
• Wu S., Liu B. Application of scintillation proximity assay in drug discovery. BioDrugs 2005; 19(6)383–392
   PubMed Web of Science ®Google Scholar
• Wu C. Y., Benet L. Z. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm. Res. 2005; 22: 11–23
   PubMed Web of Science ®Google Scholar
• Xie W., Barwick J. L., Simon C. M., Pierce A. M., Safe S., Blumberg B., Guzelian P. S., Evans R. M. Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev. 2000; 14(23)3014–3023
   PubMed Web of Science ®Google Scholar
• Yamada S., Otto P. S., Kennedy D. L., Whayne T. F., Jr. The effects of dexamethasone on metabolic activity of hepatocytes in primary monolayer culture. In Vitro. 1980; 16(7)559–570
   PubMedGoogle Scholar
• Yamamoto Y, Nakajima M, Yamazaki H, Yokoi T. Cytotoxicity and apoptosis produced by troglitazone in human hepatoma cells. Life Sci. 2001; 70(4)471–482
   PubMed Web of Science ®Google Scholar
• Yamashiro W., Maeda K., Hirouchi M., Adachi Y., Hu Z., Sugiyama Y. Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans. Drug Metab. Dispos. 2006; 34(7)1247–1254
   PubMed Web of Science ®Google Scholar
• Yoshitomi S., Ikemoto K., Takahashi J., Miki H., Namba M., Asahi S. Establishment of the transformants expressing human cytochrome P450 subtypes in HepG2, and their applications on drug metabolism and toxicology. Toxicol. In Vitro. 2001; 15(3)245–256
   PubMed Web of Science ®Google Scholar
• Zhang Y., Benet L. Z. Characterization of P-glycoprotein mediated transport of K02, a novel vinylsulfone peptidomimetic cysteine protease inhibitor, across MDR1-MDCK and Caco-2 cell monolayers. Pharm. Res. 1998; 15(10)1520–1524
   PubMed Web of Science ®Google Scholar
• Zhao P., Kunze K. L., Lee C. A. Evaluation of time-dependent inactivation of CYP3A in cryopreserved human hepatocytes. Drug Metab. Dispos. 2005; 33(6)853–861
   PubMed Web of Science ®Google Scholar
• Zhao Y., Glesne D., Huberman E. A human peripheral blood monocyte-derived subset acts as pluripotent stem cells. Proc. Natl. Acad. Sci. USA 2003; 100: 2426–2431
   PubMed Web of Science ®Google Scholar
• Zimmerman H. J. Hepatic Injury Associated with Nonsteroidal Anti-Inflammatory Drugs. Nonsteroidal Anti-Inflammatory Drugs: Mechanisms and Clinical Uses 2nd. Marcel Dekker, Inc., New York, NY 1994
   Google Scholar
• Zuber R., Anzenbacherova E., Anzenbacher P. Cytochromes P450 and experimental models of drug metabolism. J. Cell. Mol. Med. 2002; 6(2)189–198
   PubMed Web of Science ®Google Scholar
• Zulewski H., Abraham E. J., Gerlach M. J., Daniel P. B., Moritz W., Muller B., Vallejo M., Thomas M. K., Habener J. F. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 2001; 50: 521–533
   PubMed Web of Science ®Google Scholar