Clinical Relevance of P-Glycoprotein in Drug Therapy

References

• Adams J. M., Cory S. The Bcl-2 protein family: arbiters of cell survival. Science 1998; 281: 1322–1326
   PubMed Web of Science ®Google Scholar
• Amidon G. L. Determination of intestinal wall permeability. Animal Models for Oral Drug Delivery in Man: In Situ and In Vivo Approaches, W. Crouthamel, A. C. Sarapu. American Pharmaceutical Association, Academy of Pharmaceutical Sciences, Washington, DC 1983; 1–25
   Google Scholar
• Artursson P., Karlsson J. Correlation between drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Commun 1991; 175: 880–885
   PubMed Web of Science ®Google Scholar
• Artursson P., Palm K., Luthman K. Caco-2 monolayers in experimental and theoretical predictions of drug transport. Adv. Drug Delivery Rev. 1996; 22: 67–84
   Web of Science ®Google Scholar
• Ashkenazi A., Dixit V. M. Death receptors: signaling and modulation. Science 1998; 281: 1305–1308
   PubMed Web of Science ®Google Scholar
• Atack J. R., Rapoport S. I., Shapiro M. B. Cerebrospinal fluid production is normal in down syndrome. Neurobiol. Aging 1998; 19: 307–309
   PubMed Web of Science ®Google Scholar
• Augustijins P. F., Bradshaw T. P., Gan L. S. L., Hendren D. R., Thakker D. R. Evidence for a polarized efflux system in Caco-2 cells capable of modulating cyclosporine A transport. Biochem. Biophys. Res. Commun 1993; 197: 360–365
   PubMed Web of Science ®Google Scholar
• Avendano C., Menendez J. C. Inhibitors of multidrug resistance to antitumor agents (MDR). Current Med. Chem. 2002; 9: 159–193
   PubMed Web of Science ®Google Scholar
• Backman J. T., Olkkola K. T., Neuvonen P. J. Rifampin drastically reduces plasma concentrations and effects of oral midazolam. Clin. Pharmacol. Ther. 1996; 59: 7–13
   PubMed Web of Science ®Google Scholar
• Beck W. T. The cell biology of multiple drug resistance. Biochem. Pharmacol. 1987; 36: 2879–2887
   PubMed Web of Science ®Google Scholar
• Beck W. T. Mechanisms of multidrug resistance in human tumor cells. The roles of P-glycoprotein, DNA topoisomerase II, and other factors. Cancer Treat. Rev. 1990; 17(suppl. A)11–20
   PubMedGoogle Scholar
• Begley D. J., Khan E. U., Rollinson C., Abbott J., Regina A., Roux F. The role of brain extracellular fluid production and efflux mechanisms in drug transport to the brain. The Blood-Brain Barrier and Drug Delivery to the CNS, D. J. Begley, M. W. Bradbury, J. Kreuter. Marcel Dekker, Inc., New York 2000; 93–108
   Google Scholar
• Benet L. Z., Cummins C. L. The drug efflux-metabolism alliance: biochemical aspects. Adv. Drug Del. Rev. 2001; 50: S3–S11
   PubMedGoogle Scholar
• Benet L. Z., Wu C.-Y., Hebert M. F., Wacher V. J. Intestinal drug metabolism and anti-transport processes: a potential paradigm shift in oral drug delivery. J. Control. Release 1996; 39: 139–143
   Web of Science ®Google Scholar
• Berger S. H., Jehn C. H., Johnson L. F., Berger F. G. Thymidylate synthase overproduction and gene amplification in fluorodeoxyuridine-resistant human cells. Mol. Pharmacol 1985; 28: 461–467
   PubMed Web of Science ®Google Scholar
• Bertilsson L., Braithwaite R., Tybring G., Garle M., Borga O. Techniques for plasma protein binding of demethylchlorimpipramine. Clin. Pharmacol. Ther 1979; 26: 265–271
   PubMed Web of Science ®Google Scholar
• Boote D. J., Dennis I. F., Twentyman P. R., Osborne R. J., Laburte C., Hensel S., Smyth J. F., Brampton M. H., Bleehen N. M. Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J. Clin. Oncol. 1996; 14: 610–618
   PubMed Web of Science ®Google Scholar
• Brightman M. W. The anatomic basis of the blood-brain barrier. Implications of the Blood-Brain Barrier and its Manipulation: Basic Science Aspects, E. A. Neuwelt. Plenum, New York 1988; Vol. 1: 53–83
   Google Scholar
• Burton P. S., Conaradi R. A., Hilgers A. R., Ho N. F. H. Evidence for a polarized efflux for peptides in the apical membrane of Caco-2 cells. Biochem. Biophys. Res. Commun. 1993; 190: 760–766
   PubMed Web of Science ®Google Scholar
• Chen C. C., Meadows B., Regis J., Kalafsky G., Fojo T., Carrasquillo J. A., Bates S. E. Detection of in vivo P-glycoprotein inhibition by PSC 833 using Tc-99m-sestamibi. Clin. Cancer Res. 1997; 3: 545–552
   PubMed Web of Science ®Google Scholar
• Chen C., Hanson E., Watson J. W., Lee J. S. P-Glycoprotein limits the brain penetration of nonsedating but not sedating H1-antagonists. Drug Metab. Dispos. 2003; 31: 312–318
   PubMed Web of Science ®Google Scholar
• Chico I., Kang M. H., Bergan R., Abraham J., Bakke S., Meadows B., Rutt A., Robey R., Choyke P., Merino M., Goldspiel B., Smith T., Steinberg S., Figg W. D., Fojo T., Bates S. Phase I study of infusion paclitaxel in combination with the P-glycoprotein antagonist PSC 833. J. Clin. Oncol. 2001; 19: 832–842
   PubMed Web of Science ®Google Scholar
• Chikhale E. G., Ng K.-Y., Burton P. S., Borchardt R. T. Hydrogen bonding potential as a determinant of the in vitro and in situ blood-brain barrier permeability of peptides. Pharm. Res. 1994; 11: 412–419
   PubMed Web of Science ®Google Scholar
• Childs S., Yeh R. L., Hui D., Ling V. Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein. Cancer Res. 1998; 58: 4160–4167
   PubMed Web of Science ®Google Scholar
• Chishty M., Reichel A., Siva J., Abbott N. J., Begley D. J. Affinity for P-glycoprotein efflux pump at the blood-brain barrier may explain the lack of CNS side effects of modern antihistamines. J. Drug. Targeting 2001; 9: 223–228
   PubMed Web of Science ®Google Scholar
• Choo E. F., Leake B., Wandel C., Imamura H., Wood A. J. J., Wilkinson G. R., Kim R. B. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab. Dispos. 2000; 28: 655–660
   PubMed Web of Science ®Google Scholar
• Chou R. C., Levy G. Effect of heparin or salicylate infusion on serum protein binding and on concentrations of phenytoin in serum, brain and cerebrospinal fluid of rats. J. Pharmacol. Exp. Ther. 1981; 210: 42–48
   Google Scholar
• Cisternino S., Rousselle C., Lorico A., Rappa G., Scherrmann J.-M. Apparent lack of Mrp1-mediated efflux at the luminal site of mouse blood-brain barrier endothelial cells. Pharm. Res. 2003; 20: 904–909
   PubMed Web of Science ®Google Scholar
• Cole S. P. C., Sparks K. E., Fraser K., Loe D. W., Grant C. E., Wilson G. M., Deeley R. G. Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res. 2003; 54: 5902–5910
   Google Scholar
• Cordon-Cardo C., O’Brien J. P., Casals D., Rittman-Grauer L., Biedler J. L., Melamed M. R., Bertino J. R. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc. Natl. Acad. Sci. USA 1989; 86: 695–698
   PubMed Web of Science ®Google Scholar
• Cordon-Cardo C., O’Brien J. P., Boccia J., Casals D., Bertino J. R., Melamed M. R. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J. Histochem. Cytochem. 1990; 38: 1277–1287
   PubMed Web of Science ®Google Scholar
• Dantzig A. H., de Alwis D. P., Burgess M. Considerations in the design and development of transport inhibitors as adjuncts to drug therapy. Adv. Drug Del. Rev. 2003; 55: 133–150
   PubMed Web of Science ®Google Scholar
• Deffie A. M., Batra J. K., Goldenberg G. J. Direct correlation between DNA topoisomerase II activity and cytotoxicity in Adriamycin-sensitive- and resistant P 388 leukemia cell lines. Cancer Res. 1989; 49: 58–62
   PubMed Web of Science ®Google Scholar
• Drescher S., Glaeser H., Murdter T., Hitzl M., Eichelbaum M., Fromm M. F. P-Glycoprotein-mediated intestinal and biliary transport in humans. Clin. Pharmacol. Ther. 2003; 73: 223–231
   PubMed Web of Science ®Google Scholar
• Dumontet C., Sikic B. I. Mechanisms of action and resistance to antitubulin agents: microtubule dynamics, drug transport, and cell death. J. Clin. Oncol. 1999; 17: 1061–1070
   PubMed Web of Science ®Google Scholar
• Efferth T., Osieka R. Clinical relevance of the MDR1gene and its gene product, P-glycoprotein, for cancer chemotherapy: a meta-analysis. Tumordiagn. u. Ther. 1993; 14: 238–243
   Web of Science ®Google Scholar
• Evan G., Littlewood T. A matter of life and cell death. Science 1998; 281: 1317–1321
   PubMed Web of Science ®Google Scholar
• Filipits M., Suchomel R. W., Dekan G., Stigibauer W., Haider K., Depisch D., Pirker R. Expression of the multidrug resistance-associated protein (MRP) gene in colorectal carcinoma. Br. J. Cancer 1997; 75: 208–212
   PubMed Web of Science ®Google Scholar
• Giaccone G., Linn S. C., Welink J., Catimel G., Stieltjes H., van der Vijgh W. J. F., Eeltink C., Vermorken J. B., Pinedo H. M. A dose-finding and pharmacokinetic study of reversal of multidrug resistance with SDZ PSC 833 in combination with doxorubicin inpatients with solid tumors. Clin. Cancer Res. 1997; 3: 2005–2015
   PubMed Web of Science ®Google Scholar
• Giannakakou P., Sackett D. L., Kang Y.-K., Zhan Z., Buters J. T. M., Fojo T., Poruchynsky M. S. Paclitaxel-resistant human ovarian cancer cells have mutant β-tubulins that exhibit impaired paclitaxel-driven polymerization. J. Biol. Chem. 1997; 272: 17118–17125
   PubMed Web of Science ®Google Scholar
• Gottesman M. M., Fojo T., Bates S. E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nature Rev. Cancer 2002; 2: 48–58
   PubMed Web of Science ®Google Scholar
• Gramatte T., Oertel R. Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil. Clin. Pharmacol. Ther. 1999; 66: 239–245
   PubMed Web of Science ®Google Scholar
• Greiner B., Eichelbaum M., Fritz P., Kreichgauer H.-P., von Richter O., Zundler J., Kroemer H. K. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J. Clin. Invest. 1999; 104: 147–153
   PubMed Web of Science ®Google Scholar
• Haas D. W., Stone J., Clough L. A., Johnson B., Spearman P., Harris V. L., Nicotera J., Johnson R. H., Raffanti S., Zhong L., Bergqwist P., Chamberlin S., Hoagland V., Ju W. D. Steady state pharmacokinetics of indinavir in cerebrospinal fluid and plasma among adults with human immunodeficiency virus type 1 infection. Clin. Pharmacol. Ther. 2000; 68: 367–374
   PubMed Web of Science ®Google Scholar
• Haas D. W., Johnson B., Nicotera J., Bailey V. L., Harris V. L., Bowles F. B., Raffanti S., Schranz J., Finn T. S., Saah A. J., Stone J. Effects of ritonavir on indinavir pharmacokinetics in cerebrospinal fluid and plasma. Antimicrob. Agents and Chemother. 2003; 47: 2131–2137
   PubMed Web of Science ®Google Scholar
• Haber M., Burkhart C. A., Regl D. L., Madafiglio J., Norris M. D., Horwitz S. B. Altered expression of Mβ2, the class II β-tubulin isotype, in a murine J774.2 cell line with a high level of taxol resistance. J. Biol. Chem. 1995; 270: 31269–31275
   PubMed Web of Science ®Google Scholar
• Hausdorff J., Fisher G. A., Halsey J., Collins H. L., Lum B. L., Brophy N. A., Duran G. E., Nix D., Pearce T., Sikic B. I. A phase I trial of etoposide with oral cyclosporin SDZ PSC 833, a modulator of multidrug resistance. Proc. Am. Soc. Clin. Oncol. 1995; 14: 181–407
   Google Scholar
• Hegmann E. J., Bauer H. C., Kerbel R. S. Expression and functional activity of P-glycoprotein in cultured cerebral capillary endothelial cells. Cancer Res. 1992; 52: 6969–6975
   PubMed Web of Science ®Google Scholar
• Hendrikse N. H., Schinkel A. H., de Vries E. G. E., Fluks E., van der Graaf W. T. A., Willemsen A. T. M., Vaalburg W., Franssen E. J. F. Complete in vivo reversal of P-glycoprotein pump function in the blood-brain barrier visualized with positron emission tomography. Br. J. Pharmacol. 1998; 124: 1413–1418
   PubMed Web of Science ®Google Scholar
• Hendrikse N. H., de Vries E. G. E., Eriks-Fluks L., van der Graaf W. T. A., Hospers G. A. P., Willemsen A. T. M., Vaalburg W., Franssen E. J. F. A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier. Cancer Res. 1999; 59: 2411–2416
   PubMed Web of Science ®Google Scholar
• Hochman J. H., Chiba M., Nishime J., Yamazaki M., Lin J. H. Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P450 3A4. J. Pharmacol. Exp. Ther. 2000; 292: 310–318
   PubMed Web of Science ®Google Scholar
• Hochman J. H., Chiba M., Yamazaki M., Tang C., Lin J. H. P-Glycoprotein-mediated efflux of indinavir metabolites in Caco-2 cells expressing cytochrome P450 3A4. J. Pharmacol. Exp. Ther. 2001; 298: 323–330
   PubMed Web of Science ®Google Scholar
• Honjo Y., Hrycyna C. A., Yan Q. W., Medina-Perez W. Y., Robey R. W., van de Laar A., Litman T., Dean M., Bates S. E. Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res. 2001; 61: 6635–6639
   PubMed Web of Science ®Google Scholar
• Horns R. C., Dower W. J., Schimke R. T. Gene amplification in a leukemia patient treated with methotrexate. J. Clin. Oncol. 1984; 2: 2–7
   PubMed Web of Science ®Google Scholar
• Hunter J., Hirst B. H., Simmons N. L. Drug absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cells. Pharm. Res. 1993a; 10: 743–749
   PubMed Web of Science ®Google Scholar
• Hunter J., Jepson M. A., Tsuruo T., Simmons N. L., Hirst B. H. Functional expression of P-glycoprotein in apical membranes of human intestinal Caco-2 cells: kinetics of vinblastine secretion and interaction with modulators. J. Biol. Chem. 1993b; 268: 14991–14997
   PubMed Web of Science ®Google Scholar
• Inaba M., Johnson R. K. Decreased retention of actinomycin D as the basis for cross-resistance in anthracycline-resistant sublines of P388 leukemia. Cancer Res. 1977; 37: 4629–4634
   PubMed Web of Science ®Google Scholar
• Inaba M., Kobayashi H., Sakurai Y., Johnson R. K. Active efflux of daunorubicin and adriamycin in sensitive and resistant sublines of P388 leukemia. Cancer Res. 1979; 39: 2200–2203
   PubMed Web of Science ®Google Scholar
• Irvine J. D., Takahashi L., Lockhart K., Cheong J., Tolan J. W., Selick H. E., Grove J. R. MDCK (Madin-Darby Canine Kidney) cells: a tool for membrane permeability screening. J. Pharm. Sci. 1999; 88: 28–33
   PubMed Web of Science ®Google Scholar
• Jang S. H., Wientjes M. G., Au J. L.-S. Interdependent effect of P-glycoprotein-mediated drug efflux and intracellular drug binding on intracellular paclitaxel pharmacokinetics: application of computational modeling. J. Pharmacol. Exp. Ther. 2003; 304: 773–780
   PubMed Web of Science ®Google Scholar
• Jann M. W., Shirley K. L., Small G. W. Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors. Clin. Pharmacokinet. 2002; 41: 719–739
   PubMed Web of Science ®Google Scholar
• Jette L., Tetu B., Beliveau R. High levels of P-glycoprotein detected in isolated brain capillaries. Biochem. Biophys. Acta 1993; 1150: 147–154
   PubMed Web of Science ®Google Scholar
• Johanson C. E. Potential for pharmacologic manipulation of the blood-cerebrospinal fluid barrier. Implications of the Blood-Brain Barrier and its Manipulation: Basic Science Aspects, E. A. Neuwelt. Plenum, New York 1988a; Vol. 1: 223–260
   Google Scholar
• Johanson C. E. Ontogeny and phylogeny of the blood-barrier. Implications of the Blood-Brain Barrier and its Manipulation: Basic Science Aspects, E. A. Neuwelt. Plenum, New York 1988b; Vol. 1: 157–198
   Google Scholar
• Jones D. R., Hall S. D., Branch R. A., Jackson E. K., Wilkinson G. R. Plasma binding and brain uptake of benzodiazepines. Protein Binding and Drug Transport, J.-P. Tillement, E. Lindenlaub. F.K. Schattauer Verlag, New York 1986; 311–332
   Google Scholar
• Juliano R. L., Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochem. Biophys. Acta 1976; 455: 152–162
   PubMed Web of Science ®Google Scholar
• Kartner N., Evernden-Porelle D., Bradley G., Ling V. Detection of P-glycoprotein in multidrug resistant cell lines by monoclonal antibodies. Nature (London) 1985; 316: 820–823
   PubMed Web of Science ®Google Scholar
• Kavallaris M., Leary J. A., Barrett J. A., Friedlander M. L. MDR1 and multidrug resistance-associated protein (MRP) gene expression in epithelial ovarian tumors. Cancer Letters 1996; 102: 7–16
   PubMed Web of Science ®Google Scholar
• Keep R. F., Jones H. C. A morphometric study on the development of the lateral ventricle choroid plexus, choroid plexus capillaries and ventricular ependyma in the rat. Dev. Brain Res. 1990; 56: 47–53
   PubMedGoogle Scholar
• Khaliq Y., Gallicano K., Venance S., Kravcik S., Cameron W. Effect of ketoconazole on ritonavir and saquinavir concentrations in plasma and cerebrospinal fluid from patients infected with human immunodeficiency virus. Clin. Pharmacol. Ther. 2000; 68: 637–646
   PubMed Web of Science ®Google Scholar
• Kim R. B., Fromm M. F., Wandel C., Leak B., Wood A. J. J., Roden D. M., Wilkinson G. R. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Invest. 1998; 101: 289–294
   PubMed Web of Science ®Google Scholar
• Kovarik J. M., Rigaudy L., Guerret M., Gerbeau C., Rost K.-L. Longitudinal assessment of a P-glycoprotein-mediated drug interaction of valspodar on digoxin. Clin. Pharmacol. Ther. 1999; 66: 391–400
   PubMed Web of Science ®Google Scholar
• Kusuhara H., Sugiyama Y. Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (part I). Drug Discov. Today 2001a; 6: 150–156
   PubMed Web of Science ®Google Scholar
• Kusuhara H., Sugiyama Y. Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (part II). Drug Discov. Today 2001b; 6: 206–212
   PubMed Web of Science ®Google Scholar
• Levin V. A. Relationship of octanol/water partition coefficient and mole-cular weight to rat brain capillary permeability. J. Med. Chem. 1980; 23: 682–684
   PubMed Web of Science ®Google Scholar
• Lin J. H., Cocchetto D., Duggan D. E. Protein binding as a primary determinant of the clinical pharmacokinetic properties of nonsteroidal anti-inflammatory drugs. Clin. Pharmacokinet. 1987; 12: 402–432
   PubMed Web of Science ®Google Scholar
• Lin J. H., Chiba M., Baillie T. A. Is the role of the small intestine in first-pass metabolism overemphasized?. Pharmacol. Rev. 1999a; 51: 135–157
   PubMed Web of Science ®Google Scholar
• Lin J. H., Chiba M., Chen I.-W., Nishime J. A., deLuna F. A., Yamazaki M., Lin Y. Effect of dexamethasone on the intestinal first-pass metabolism of indinavir in rats. Evidence of cytochrome P450 3A and P-glycoprotein induction. Drug Metab. Dispos. 1999b; 27: 1187–1193
   PubMed Web of Science ®Google Scholar
• Lin J. H., Yamazaki M. Role of P-glycoprotein in pharmacokinetic: clinical implications. Clin. Pharmacokinet 2003; 42: 59–98
   PubMed Web of Science ®Google Scholar
• Lin T. H., Lin J. H. Effects of protein binding and experimental disease states on brain uptake of benzodiazepines in rats. J. Pharmacol. Exp. Ther. 1990; 253: 45–50
   PubMed Web of Science ®Google Scholar
• Liu Y.-Y., Han T.-Y., Giuliano A. E., Hansen N., Cabot M. C. Uncoupling ceramide glycosylation by transfection of glucosylceramide synthase antisense reverses adriamycin resistance. J. Biol. Chem. 2000; 275: 7138–7143
   PubMed Web of Science ®Google Scholar
• Liu Y.-Y., Han T.-Y., Giuliano A. R., Cabot M. C. Ceramide glycosylation potentiates cellular multidrug resistance. FASEB J. 2001; 15: 719–730
   PubMed Web of Science ®Google Scholar
• Loe D. W., Deeley R. G., Cole S. P. C. Characterization of vincristine transport by the Mr 190,000 multidrug resistance protein (MRP). Evidence for cotransport with reduced glutathione. Cancer Res. 1998; 58: 5130–5136
   PubMed Web of Science ®Google Scholar
• Lum B. L., Kaubisch S., Yahanda A. M., Adler K. M., Jew L., Ehsan M. N., Brophy N. A., Halsey J., Gosland M. P., Sikic B. I. Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J. Clin. Oncol. 1992; 10: 1635–1642
   PubMed Web of Science ®Google Scholar
• Macey R. I. Mathematical models of membrane transport processes. Physiology of membrane Disorders, R. Andreoli. Plenum Press, New York 1978; 125–146
   Google Scholar
• Mahar Doan K. M., Humphreys J. E., Webster L. O., Wring S. A., Shampine L. J., Serabjit-Singh C. J., Adkison K. K., Polli J. W. Passive permeability and P-glycoprotein mediated efflux differentiate CNS and nonCNS marketed drugs. J. Pharmacol. Exp. Ther. 2002; 303: 1029–1037
   PubMed Web of Science ®Google Scholar
• Maliepaard M., van Gastelen M. A., de Jong L. A., Pluim D., van Waardenburg R. C. A. M., Ruevekamp-Helmers M. C., Foot B. G. J., Schellens J. H. M. Overexpression of the BCRP/MXR/ ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res. 1999; 59: 4559–4563
   PubMed Web of Science ®Google Scholar
• Mayer U., Wagenaar E., Dorobek B., Benijnen J. H., Borst P., Schinkel A. H. Full blockade of intestinal P-glycoprotein and extensive inhibition blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833. J. Clin. Invest. 1997; 100: 2430–2436
   PubMed Web of Science ®Google Scholar
• McTavish D., Sorkin E. M. Verapamil. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs 1989; 38: 19–76
   PubMed Web of Science ®Google Scholar
• Nishino J., Suzuki H., Sugiyama D., Kitazawa T., Ito K., Hanano M., Sugiyama Y. Transepithelial transport of organic anions across the choroid plexus: possible involvement of organic anion transporter and multidrug resistance-associated protein. J. Pharmacol. Exp. Ther. 1999; 290: 289–294
   PubMed Web of Science ®Google Scholar
• Nooter K. Brutel, de la Riviere G., Look M. P., van Wingerden K. E., Henzen-Logmans S. C., Scheper R. J., Flens M. J., Klijn J. G. M., Stoter G., Foekens J. A. The prognostic significance of expression of the multidrug resistance-associated protein (MRP) in primary breast cancer. Br. J. Cancer 1997b; 76: 486–493
   PubMed Web of Science ®Google Scholar
• Nooter K., Brutel de la Riviere G., Klijn J., Stoter G., Foekens J. Multidrug resistance protein in recurrent breast cancer. Lancet 1997a; 349: 1885–1886
   PubMed Web of Science ®Google Scholar
• Nooter K., Kok T., Bosman F. T., van Wingerden K. E., Stoter G. Expression of the multidrug resistance protein (MRP) in squamous cell carcinoma of oesophagus and response to pre-operative chemotherapy. Eur. J. Cancer 1998; 34: 81–86
   PubMed Web of Science ®Google Scholar
• Olkkola K. T., Backman J. T., Neuvonen P. J. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin. Pharmacol. Ther. 1994; 55: 481–485
   PubMed Web of Science ®Google Scholar
• Ooi H., Colucci W. S. Pharmacological treatment of heart failure. Goodman & Gillman's The Pharmacological Basis of Therapeutics 10th ed., J. G. Hardamn, L. E. Limbird. McGraw-Hill, New York 2001; 901–932
   Google Scholar
• Ozols R. F., Cunnion R. E., Klecker R. W. Jr., Hamilton T. C., Ostchega Y., Parrillo J. E., Young R. C. Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients. J. Clin. Oncol. 1987; 5: 641–647
   PubMed Web of Science ®Google Scholar
• Pade V., Stavchansky S. Estimation of the relative contribution of transcellular and paracellular pathway to the transport of passively absorbed drugs in the Caco-2 cell culture model. Pharm. Res. 1997; 14: 1210–1215
   PubMed Web of Science ®Google Scholar
• Pardridge W. M. Transport of protein-bound hormones into tissue in vivo. Endocr. Rev. 1981; 2: 103–123
   PubMed Web of Science ®Google Scholar
• Pardridge W. M., Frank H. J. L., Cornford E. M., Braun L. D., Crane P. D., Oldendorf W. H. Neuropeptides and blood-brain barrier. Adv. Biochem. Psychopharmacol. 1981; 28: 321–328
   PubMedGoogle Scholar
• Polli J. W., Jarrett J. L., Studenberg S. D., Humphreys J. E., Dennis S. W., Brouwer K. R., Woolley J. L. Role of P-glycoprotein on CNS disposition of amprenavir (141W94), an HIV protease inhibitor. Pharm. Res. 1999; 16: 1206–1212
   PubMed Web of Science ®Google Scholar
• Polli J. W., Wring S. A., Humphreys J. E., Huang L., Morgan J. B., Webster L. O., Serabjit-Singh C. S. Rational use of in vitro P-glycoprotein assays in drug discovery. J. Pharmacol. Exp. Ther. 2001; 299: 620–628
   PubMed Web of Science ®Google Scholar
• Raffanti S., Haas D. W. Antiretroviral agents. Goodman & Gillman's The Pharmacological Basis of Therapeutics. 10th ed., J. G. Hardamn, L. E. Limbird. McGraw-Hill, New York 2001; 1349–1380
   Google Scholar
• Rao V. V., Dahlheimer J. L., Bardgett M. E., Snyder A. Z., Finch R. A., Sartorelli A. C., Piwnica-Worms D. Choroid plexus epithelial expression of MDR1 P-glycoprotein and multidrug resistance-associated protein contribute to blood-cerebrospinal-fluid drug permeability barrier. Proc. Natl. Acad. Sci. USA 1999; 96: 3900–3905
   PubMed Web of Science ®Google Scholar
• Rapport S. I. Transport in cells and tissues. Blood-brain Barrier in Physiology and Medicine, S. I. Rapport. Raven Press, New York 1976; 17–42
   Google Scholar
• Regina A., Koman A., Piciotti M., Hafny B. E., Center M. S., Bergmann R., Couraud P. O., Roux F. Mrp1 multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells. J. Neurochem. 1998; 71: 705–715
   PubMed Web of Science ®Google Scholar
• Robinson P. J., Rapoport S. I. Kinetics of protein binding determines rates of uptake of drugs by brain. Am. J. Physiol. 1986; 251: R1212–R1220
   PubMed Web of Science ®Google Scholar
• Rowinsky E. K., Smith L., Wang Y.-M., Chaturvedi P., Villalona M., Campbell E., Aylesworth C., Eckhardt S. G., Hammond L., Kraynak M., Drengler R., Stephenson J. Jr., Harding M. W., Von Hoff D. D. Phase I and pharmacokinetic study of paclitaxel in combination with biricodar (VX-710), a novel agent that reverses multidrug resistance conferred by overexpression of both MDR1 and MRP. J. Clin. Oncol. 1998; 16: 2964–2976
   PubMed Web of Science ®Google Scholar
• Rowley M., Kulagowski J. J., Watt A. P., Rathbone D., Stevenson G. I., Carling R. W., Baker R., Marshall G. R., Kemp J. A., Foster A. C., Grimwood S., Hargreaves R., Hurley C., Saywell E. L., Tricklebank M. D., Leeson P. D. Effect of plasma protein binding on in vivo activity and brain penetration of glycine/NMDA receptor antagonists. J. Med. Chem. 1997; 40: 4053–4068
   PubMed Web of Science ®Google Scholar
• Sadeque A. J. M., Wandel C., He H., Shah S., Wood A. J. J. Increased drug delivery to the brain by P-glycoprotein inhibition. Clin. Pharmacol. Ther. 2000; 68: 231–237
   PubMed Web of Science ®Google Scholar
• Schellens J. H. M., Kruytzer M. F., Vasey P. A., Harris A. L., Deplanque G., Burgess M., de Alwis D., O’Callaghan M., Kaye S. B., Beijnen J. H. Phase I and pharmacokinetic study of the P-glycoprotein inhibitor LY335979 and paclitaxel in patients with solid tumors. Am. Assoc. Cancer Res. 2001; 42: 535, Abstract #2882
   Google Scholar
• Schimke R. T. Gene amplification, drug resistance, and cancer. Cancer Res. 1984; 44: 1735–1742
   PubMed Web of Science ®Google Scholar
• Schinkel A. H., Smit J. J. M., van Tellingen O., Beijnen J. H., Wagnaar E., van Deemter L., Mol C. A. A. M., van der Valk M. A., Robanus-Maandag E. C., te Riele H. P. J., Berns A. J. M., Borst P. Disruption of the mouse mdr 1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994; 77: 491–502
   PubMed Web of Science ®Google Scholar
• Schinkel A. H., Wagenaar E., van Deemter L., Mol C. A. A. M., Borst P. Absence of the mdr1a P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J. Clin. Invest. 1995; 96: 1698–1705
   PubMed Web of Science ®Google Scholar
• Schinkel A. H., Wagenaar E., Mol C. A., van Deemter L. P-Glycoprotein in blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J. Clin. Invest. 1996; 97: 2517–2524
   PubMed Web of Science ®Google Scholar
• Schinkel A. H., Mayer U., Wagenaar E., Mol C. A. A. M., van Deemter L., Smit J. J. M., van der Valk M. A., Voordouw A. C., Sprits H., van Tellingen O., Zijlmans J. M. J. M., Fibbe W. E., Borst P. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc. Natl. Acad. Sci. USA 1997; 94: 4028–4033
   PubMed Web of Science ®Google Scholar
• Seetharaman S., Barrand M. A., Maskell L., Scheper R. J. Multidrug resistance-related transport proteins in isolated human brain microvessels and in cells cultured from these isolates. J. Neurochem. 1998; 70: 1151–1159
   PubMed Web of Science ®Google Scholar
• Sirotnak F. M., Moccio D. M., Kelleher L. E., Goutas L. J. Relative frequency and kinetic properties of transport-defective phenotypes among methotrexate-resistant L1210 clonal cell lines derived in vivo. Cancer Res. 1981; 41: 4447–4452
   PubMed Web of Science ®Google Scholar
• Sobrero A. F., Moir R. D., Bertino J. R., Handschumacher R. E. Defective facilitated diffusion of nucleosides, a primary mechanism of resistance to 5-fluoro-2′-deoxyuridine in HCT-8 human carcinoma line. Cancer Res. 1985; 45: 3155–3160
   PubMed Web of Science ®Google Scholar
• Sparreboom A., van Asperen J., Mayer U., Schinkel A. H., Smit J. W., Meijer D. K. F., Borst P., Nooijen W. J., Beijen J. H., van Tellingen O. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc. Natl. Acad. Sci. USA 1997; 94: 2031–2035
   PubMed Web of Science ®Google Scholar
• Sparreboom A., Planting A. S. T., Jewell R. C., van der Burg M. E., van der Gaast A., de Bruijn P., Loos W. J., Nooter K., Chandler L. H., Paul E. M., Wissel P. S., Verweij J. Clinical pharmacokinetics of doxorubicin in combination with GF120918, a potent inhibitor of MDR1 P-glycoprotein. Anticancer Drugs 1999; 10: 719–728
   PubMed Web of Science ®Google Scholar
• Sun H., Dai H., Shaik N., Elmquist W. F. Drug efflux transporters in the CNS. Adv. Drug Del. Rev. 2003; 55: 83–105
   PubMed Web of Science ®Google Scholar
• Takebayashi Y., Akiyama S., Natsugoe S., Hokita S., Niwa K., Kitazono M., Sumizawa T., Tani A., Furukawa T., Aikou T. The expression of multidrug resistance protein in human gastrointestinal tract carcinomas. Cancer 1998; 82: 661–666
   PubMed Web of Science ®Google Scholar
• Tamai I., Tsuji A. Transporter-mediated permeation of drugs across the blood-brain barrier. J. Pharm. Sci. 2000; 89: 1371–1388
   PubMed Web of Science ®Google Scholar
• Tanaka H., Mizojiri K. Drug-protein binding and blood-brain barrier permeability. J. Pharmacol. Exp. Ther. 1999; 288: 912–918
   PubMed Web of Science ®Google Scholar
• Tew K. D., Houghton P. J., Houghton J. A. Modulation of glutathione. Preclinical and Clinical Modulation of Anticancer Drugs. CRC press, Boca Raton 1993; 13–77
   Google Scholar
• Thiebaut F., Tsuruo T., Hamada H., Gottesman M. M., Pastan I., Willingham M. C. Cellular localization of the multidrug resistance gene product P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. USA. 1987; 84: 7735–7738
   PubMed Web of Science ®Google Scholar
• Thiebaut F., Tsuruo T., Hamada H., Gottesman M. M., Pastan I., Willingham M. C. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein. J. Histochem. Cytochem. 1989; 37: 159–164
   PubMed Web of Science ®Google Scholar
• Thomas H., Steiner J. A., Mould G. P., Mellow G., Stewart A. J., Norris D. B., Waterfall J. F. A phase IIA pharmacokinetic study of the P-glycoprotein inhibitor, XR9576 in combination with paclitaxel in patients with ovarian cancer. Am. Soc. Clin. Oncol 2001, abstract #288
   PubMed Web of Science ®Google Scholar
• Trent J. M., Buick R. N., Olson S., Horns R. C. Jr., Schimke R. T. Cytologic evidence for gene amplification in methotrexate-resistant cells obtained from a patient with ovarian adenocarcinoma. J. Clin. Oncol. 1984; 2: 8–15
   PubMed Web of Science ®Google Scholar
• Tsuji A., Terasaki T., Takabatake Y., Tenda Y., Tamai I., Yamashima T., Moritani S., Tsuruo T., Yamashita J. P-Glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Life Sci. 1992; 51: 1427–1437
   PubMed Web of Science ®Google Scholar
• Tsuruo T., Iida H., Tsukagoshi S., Sakurai Y. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res. 1981; 41: 1967–1972
   PubMed Web of Science ®Google Scholar
• Ueda C. T., Williamson B. J., Dzindzio B. S. Absolute quinidine bioavailability. Clin. Pharmacol. Ther. 1976; 20: 260–265
   PubMed Web of Science ®Google Scholar
• Ueda C. T., Lemaire M., Gsell G., Misslin P., Nussbaumer K. Apparent dose dependent oral absorption of cyclosporine A in rats. Biopharm. Drug Dispos. 1984; 5: 141–151
   PubMed Web of Science ®Google Scholar
• Unadkat J. D. Presentation at AAPS Transporter Workshop. Peachtree, GA Feb., 2003; 10–12
   Google Scholar
• van Asperen J., van Tellingen O., Tijssen F., Schinkel A. H., Beijnen J. H. Increased accumulation of doxorubicin and doxorubicinol in cardiac tissue of mice lacking mdr1a P-glycoprotein. Br. J. Cancer 1999; 79: 108–113
   PubMed Web of Science ®Google Scholar
• van de Waterbeemd H. Intestinal permeability: prediction from theory. Oral Drug Absorption: Prediction and Assessment, J. B. Dressman, H. Lennernas. Marcel Dekker Inc., New York 2000; 31–49
   Google Scholar
• Van Zuylen L., Nooter K., Sparreboom A., Verweij J. Development of multidrug resistance convertors: sense or nonsense? Invest. New Drugs 2000; 18: 205–220
   Web of Science ®Google Scholar
• Verstuyft C., Strabach S., El Morabet H., Kerb R., Brinkmann U., Dubert L., Jaillon P., Funck-Brentano C., Trugnan G., Becquemont L. Dipyridamole enhances digoxin bioavailability via P-glycoprotein inhibition. Clin. Pharmacol. Ther. 2003; 73: 51–60
   PubMed Web of Science ®Google Scholar
• Wandel C., Kim R. B., Guengerich F. P., Wood A. J. J. Mibefradil is a P-glycoprotein substrate and a potent inhibitor of both P-glycoprotein and CYP3A in vitro. Drug Metab. Dispos. 2000; 28: 895–898
   PubMed Web of Science ®Google Scholar
• Webb M., Brun M., McNiven M., Le Couteur D., Craft P. MDR1 and MRP expression in chronic B-cell lymphoproliferative disorders. Br. J. Haematology 1998; 102: 710–717
   PubMed Web of Science ®Google Scholar
• Westphal K., Weinbrenner A., Zschiesche M., Franke G., Knoke M., Oertel R., Fritz P., von Richter O., Hachenberg T., Warzok R., Kauffmann H.-M., Schrenk D., Terhaag B., Kroemer H., Siegmund W. Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction. Clin. Pharmacol. Ther. 2000; 68: 345–355
   PubMed Web of Science ®Google Scholar
• Wetterich U., Sphn-Langguth H., Mutschler E., Terhaag B., Rosch W., Langguth P. Evidence for intestinal secretion as an additional clearance pathway of talinolol enantiomers: concentration- and dose-dependent absorption in vitro and in vivo. Pharm. Res. 1996; 13: 514–522
   PubMed Web of Science ®Google Scholar
• Wijnholds J., de Lange E. C. M., Scheffer G. L., van den Berg D.-J., Mol C. A. A. M., van der Valk M., Schinkel A. H., Scheper R. J., Breimer D. D., Borst P. Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. J. Clin. Invest. 2000; 105: 279–285
   PubMed Web of Science ®Google Scholar
• Wilson C. G., Washington N. Small intestine: transit and absorption of drugs. Physiological Pharmaceutics: Biological Barriers to Drug absorption, C. G. Wilson, N. Washington. Ellis Horwood Ltd., Chichester 1989; 71–90
   Google Scholar
• Yamazaki M., Neway W. E., Ohe T., Chen I.-W., Rowe J. F., Hochman J. H., Chiba M., Lin J. H. In vitro substrate identification studies for P-glycoprotein mediated transport: species differences and predictability of in vitro results. J. Pharmacol. Exp. Ther. 2001; 296: 723–735
   PubMed Web of Science ®Google Scholar
• Yokogawa K., Takahashi M., Tamai I., Konishi H., Nomura M., Moritani S., Miyamoto K., Tsuji A. P-Glycoprotein-dependent disposition kinetics of tacrolimus: studies in mdr1a knockout mice. Pharm. Res. 1999; 16: 1213–1218
   PubMed Web of Science ®Google Scholar