Role of efflux pumps and metabolising enzymes in drug delivery

Bibliography

• WACHER VJ, WU CY, BENET LZ: Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. MoL Carcinog (1995) 13(3):129–134.
   Google Scholar
• ••An excellent overview of efflux pumps andmetabolic enzymes.
   Google Scholar
• HOLLAND TB, BLIGHT MA: ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans. J. MoL Biol. (1999) 293(2):381–399.
   Google Scholar
• LEGARE D, RICHARD D, MUKHOPADHYAY R et al: The leishmania ATP-binding cassette protein PGPA is an intracellular metal-thiol transporter ATPase. j Biol. Chem. (2001) 276(28):26301–26307.
   Google Scholar
• BAKOS E, HEGEDUS T, HOLLO Z et al.: Membrane topology and glycosylation of the human multidrug resistance-associated protein. J. Biol. Chem. (1996) 271(21):12322–12326.
   Google Scholar
• HIPFNER DR, ALMQUIST KC, LESLIE EM et al.: Membrane topology of the multidrug resistance protein (MRP). A study of glycosylation-site mutants reveals an extracytosolic NH2 terminus. J. Biol. Chem. (1997) 272(38):23623–23630.
   Google Scholar
• KAST C, GROS P: Topology mapping of the amino-terminal half of multidrug resistance-associated protein by epitope insertion and immunofluorescence. J. Biol. Chem. (1997) 272(42):26479–26487.
   Google Scholar
• KAGE K, TSUKAHARA S, SUGIYAMA T et al.: Dominant-negative inhibition of breast cancer resistance protein as drug efflux pump through the inhibition of S-S dependent homodimerization. Int. J. Cancer (2002) 97(5):626–630.
   Google Scholar
• URBATSCH IL, SANKARAN B, BHAGAT S, SENIOR AE: Both P-glycoprotein nucleotide-binding sites are catalytically active. J. Biol. Chem. (1995) 270(45):26956–26961.
   Google Scholar
• GOTTESMAN MM, AMBUDKAR SV: Overview: ABC transporters and human disease. J. Bioenerg Biomembr. (2001) 33(6):453–458.
   Google Scholar
• ••An excellent overview of ABC transporters.
   Google Scholar
• JULIANO RL, LING V: A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta. (1976) 455(1):152–162.
   Google Scholar
• RAVIV Y, POLLARD HB, BRUGGEMANN EP, PASTAN I, GOTTESMAN MM: Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells. J. Biol. Chem. (1990) 265(7):3975–3980.
   Google Scholar
• AMBUDKAR SV, DEY S, HRYCYNA CA et al.: Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Ann. Rev. Pharmacol. ToxicoL (1999) 39:361–398.
   Google Scholar
• ••An excellent overview of ABC transporters.
   Google Scholar
• AUNGST BJ: P-glycoprotein, secretory transport, and other barriers to the oral delivery of anti-HIV drugs. Adv. Drug Deliv. Rev. (1999) 39(1-3):105–116.
   Google Scholar
• SUZUKI H, SUGIYAMA Y: Role of metabolic enzymes and efflux transporters in the absorption of drugs from the small intestine. Eur. j Pharm. Sci. (2000) 12(1):3–12.
   Google Scholar
• THIEBAUT F, TSURUO T, HAMADA H et al.: Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. NatL Acad. Sci. USA (1987) 84(20:7735–7738.
   Google Scholar
• CORDON-CARDO C, O'BRIEN JP, CASALS D et al: Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc. Nail. Acad. Sci. USA (1989) 86(2):695–698.
   Google Scholar
• SUGAWARA I, KATAOKA I, MORISHITA Yet al.: Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody, MRK 16. Cancer Res. (1988) 48(7):1926–1929.
   Google Scholar
• LOO TW, CLARKE DM: Location of the rhodamine-binding site in the human multidrug resistance P-glycoprotein. j Biol. Chem. (2002) 277(46):44332–44338.
   Google Scholar
• LOO TW, CLARKE DM: Vanadate trapping of nucleotide at the ATP-binding sites of human multidrug resistance P-glycoprotein exposes different residues to the drug-binding site. Proc. NatL Acad. Sci. USA (2002) 99(6):3511–3516.
   Google Scholar
• HIGGINS CF, GOTTESMAN MM: Is the multidrug transporter a flippase? Trends Biochem. Sci. (1992) 17(1):18–21.
   Google Scholar
• EYTAN GD, KUCHEL PW: Mechanism of action of P-glycoprotein in relation to passive membrane permeation. Int. Rev. CytoL (1999) 190:175–250.
   Google Scholar
• SHAROM FJ: The Pglycoprotein efflux pump: how does it transport drugs? Membr. Biol. (1997) 160(3):161–175.
   Google Scholar
• MARTIN C, BERRIDGE G, HIGGINS CF et al: Communication between multiple drug binding sites on P-glycoprotein. Mol. PharmacoL (2000) 58(3):624–632.
   Google Scholar
• DEY S, RAMACHANDRA M, PASTAN I, GOTTESMAN MM, AMBUDKAR SV: Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proc. Natl. Acad. Sci. USA (1997) 94(20):10594–10599.
   Google Scholar
• DIDZIAPETRIS R, JAPERTAS P, AVDEEF A, PETRAUSKAS A: Classification analysis of P-glycoprotein substrate specificity. J. Drug Target (2003) 11(7):391–406.
   Google Scholar
• FAN K, FAN D, CHENG LF, LI C: Expression of multidrug resistance-related markers in gastric cancer. Anticancer Res. (2000) 20(6C):4809–4814.
   Google Scholar
• AMPOS L, GUYOTAT D, ARCHIMBAUD E et al.: Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood (1992) 79(2):473–476.
   Google Scholar
• CUMBER PM, JACOBS A, HOY T et al: Expression of the multiple drug resistance gene (mdr-1) and epitope masking in
   Google Scholar
• ••chronic lymphatic leukaemia. Br. J. Haematol (1990) 76(2):226–230.
   Google Scholar
• VERRELLE P, MEISSONNIER F, FONCK Yet al.: Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma. J. Natl Cancer Inst. (1991) 83(2):111–116.
   Google Scholar
• MARIE JP, ZHOU DC, GURBUXANI S, LEGRAND 0, ZITTOUN R: MDR1/ P-glycoprotein in haematological neoplasms. Eur. j Cancer (1996) 32A(6):1034–1038.
   Google Scholar
• FOJO AT, UEDA K, SLAMON DJ et al.: Expression of a multidrug-resistance gene in human tumors and tissues. Proc. Nail. Acad. Sci. USA (1987) 84(1):265–269.
   Google Scholar
• FOJO AT, SHEN DW, MICKLEY LA, PASTAN I, GOTTESMAN MM: Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug-resistance gene. J. Clin. Oncol (1987) 5(12):1922–1927.
   Google Scholar
• FARDEL O, LECUREUR V, GUILLOUZO A: The P-glycoprotein multidrug transporter. Gen. Pharmacol (1996) 27(8):1283–1291.
   Google Scholar
• KANT E, HEIDE I, THIEDE C, HERRMANN R, ROCHLITZ CF: MDR1 expression correlates with mutant p53 expression in colorectal cancer metastases. J. Cancer Res. Clin. Oncol. (1996) 122(11):671–675.
   Google Scholar
• HSU CH, CHEN CL, HONG RL et al: Prognostic value of multidrug resistance 1, glutathione-S-transferase-pi and p53 in advanced nasopharyngeal carcinoma treated with systemic chemotherapy. Oncology (2002) 62(4):305–312.
   Google Scholar
• ISRAELI D, ZIAEI S, GONIN P, GARCIA L: A proposal for the physiological significance of mdrl and Bcrp 1 /Abcg2 gene expression in normal tissue regeneration and after cancer therapy. Theor. Bid. (2005) 232(1):41–45.
   Google Scholar
• HUNTER J, JEPSON MA, TSURUO T, SIMMONS NL, HIRST BH: Functional expression of P-glycoprotein in apical membranes of human intestinal Caco-2 cells. Kinetics of vinblastine secretion and interaction with modulators./ Biol. Chem. (1993) 268(20):14991–14997.
   Google Scholar
• HUNTER J, HIRST BH, SIMMONS NL: Drug absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers. Pharm. Res. (1993) 10(5):743–749.
   Google Scholar
• SPARREBOOM A, VAN ASPEREN MAYER U et al.: Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc. Natl. Acad. Sci. USA (1997) 94(5):2031–2035.
   Google Scholar
• KIM RB, FROMM MF, WANDEL C et al.: The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Invest. (1998) 101(2):289–294.
   Google Scholar
• TERAO T, HISANAGA E, SAI Y, TAMAI I, TSUJI A: Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier. J. Pharm. Pharmacol (1996) 48(10):1083–1089.
   Google Scholar
• RAMAKRISHNAN P: The role of P-glycoprotein in the blood-brain barrier. Einstein Quart. J. Biol. Med. (2003) 19:160–165.
   Google Scholar
• VOGELGESANG S, WARZOK RW, CASCORBI I et al: The role of P-glycoprotein in cerebral amyloid angiopathy; implications for the early pathogenesis of Alzheimer's disease. Current Alzheimer Research (2004) 1(2):121–125.
   Google Scholar
• POTSCHKA H, LOSCHER W: In vivo evidence for P-glycoprotein-mediated transport of phenytoin at the blood-brain barrier of rats. Epi/epsia (2001) 42(10):1231–1240.
   Google Scholar
• WACHER VJ, SILVERMAN JA, ZHANG Y, BENET LZ: Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. j Pharm. Sci. (1998) 87(11):1322–1330.
   Google Scholar
• VAN ASPEREN VAN TELLINGEN 0, SPARREBOOM A et al: Enhanced oral bioavailability of paclitaxel in mice treated with the P-glycoprotein blocker SDZ PSC 833. Br. J. Cancer (1997) 76(9):1181–1183.
   Google Scholar
• •This paper demonstrates classic examples of P-gp inhibitors strategies.
   Google Scholar
• GAN LS, MOSELEY MA, KHOSLA B et al.: CYP3A-like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells. Drug Metab. Dispos. (1996) 24(3):344–349.
   Google Scholar
• RAEISSI SD, HIDALGO IJ, SEGURA-AGUILAR J, ARTURSSON P: Interplay between CYP3A-mediated metabolism and polarized efflux of terfenadine and its metabolites in intestinal epithelial Caco-2 (TC7) cell monolayers. Pharm. Res. (1999) 16(5):625–632.
   Google Scholar
• ••An excellent overview of efflux pumps and metabolic enzymes.
   Google Scholar
• SU SF, HUANG JD: Inhibition of the intestinal digoxin absorption and exsorption by quinidine. Drug Metab. Dispos. (1996) 24(2):142–147.
   Google Scholar
• KUSUHARA H, SUZUKI H, SUGIYAMA Y: The role of P-glycoprotein and canalicular multispecific organic anion transporter in the hepatobiliary excretion of drugs. J. Pharm. Sci. (1998) 87(9):1025–1040.
   Google Scholar
• LYUBIMOV E, LAN LB, PASHINSKY I, STEIN WD: Effect of modulators of the multidrug resistance pump on the distribution of vinblastine in tissues of the mouse. Anticancer Drugs (1996) 7(1):60–69.
   Google Scholar
• GONZALEZ O, COLOMBO T, DE FUSCO M et al.: Changes in doxorubicin distribution and toxicity in mice pretreated with the cyclosporin analogue SDZ PSC 833. Cancer Chemother. Pharmacol (1995) 36(4):335–340.
   Google Scholar
• SCHUETZ EG, SCHINKEL AH, RELLING MV, SCHUETZ JD: P-glycoprotein: a major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans. Proc. Natl Acad. Sci. USA (1996) 93(9):4001–4005.
   Google Scholar
• HORI R, OKAMURA N, MBA T, TANIGAWARA Y: Role of P-glycoprotein in renal tubular secretion of digoxin in the isolated perfused rat kidney. J. Pharmacol. Exp. Ther. (1993) 266(3):1620–1625.
   Google Scholar
• ITO T, YANO I, TANAKA K, INUI KI: Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1. Pharmacol Exp. Ther. (1997) 282(2):955–960.
   Google Scholar
• ZAMAN GJ, FLENS MJ, VAN LEUSDEN MR et al: The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump. Proc. Natl Acad. Sci. USA (1994) 91(19):8822–8826.
   Google Scholar
• KRISHNAMACHARY N, CENTER MS: The MRP gene associated with a non-P-glycoprotein multidrug resistance encodes a 190-1cDa membrane bound glycoprotein. Cancer Res. (1993) 53(16):3658–3661.
   Google Scholar
• DOLFINI E, DASDIA T, ARANCIA G et al.: Characterization of a clonal human colon adenocarcinoma line intrinsically resistant to doxorubicin. Br. J. Cancer (1997) 76(1):67–76.
   Google Scholar
• CHEN ZS, FURUKAWA T, SUMIZAWA T et al.: ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Md. PharmacoL (1999) 55(5):921–928.
   Google Scholar
• JEDLITSCHKY G, BURCHELL B, KEPPLER D: The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J. Biol. Chem. (2000) 275(39):30069–30074.
   Google Scholar
• LEIER I, JEDLITSCHKY G, BUCHHOLZ U et al.: The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J. Biol. Chem. (1994) 269(45):27807–27810.
   Google Scholar
• STRIDE BD, GRANT CE, LOE DW et al.: Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Md. PharmacoL (1997) 52(3):344–353.
   Google Scholar
• EVERS R, ZAMAN GJ, VAN DEEMTER Let al.: Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells. J. Clin. Invest. (1996) 97(5):1211–1218.
   Google Scholar
• FLENS MJ, ZAMAN GJ, VAN DER VALK P et al: Tissue distribution of the multidrug resistance protein. Am. J. PathoL (1996) 148(4):1237–1247.
   Google Scholar
• VAN LUYN MULLER M, RENES J et al.: Transport of glutathione conjugates into secretory vesicles is mediated by the multidrug-resistance protein 1. Int. J. Cancer (1998) 76(1):55–62.
   Google Scholar
• LOE DW, STEWART RK, MASSEY TE, DEELEY RG, COLE SP: ATP-dependent transport of aflatoxin B1 and its glutathione conjugates by the product of the multidrug resistance protein (MRP) gene. MoL Pharmacol (1997) 51(6):1034–1041.
   Google Scholar
• BURGER H, FOEKENS JA, LOOK MP et al.: RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: correlation with chemotherapeutic response. Clin. Cancer Res. (2003) 9(2):827–836.
   Google Scholar
• OHISHI Y, ODA Y, UCHIUMI T et al: ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma. Clin. Cancer Res. (2002) 8(12):3767–3775.
   Google Scholar
• PLASSCHAERT SL, VELLENGA E, DE BONT ES et al.: High functional P-glycoprotein activity is more often present in T-cell acute lymphoblastic leukaemic cells in adults than in children. Leuk. Lymphoma (2003) 44(1):85–95.
   Google Scholar
• PEI QL, KOBAYASHI Y, TANAKA Y et al.: Increased expression of multidrug resistance-associated protein 1 (mrpl) in hepatocyte basolateral membrane and renal tubular epithelia after bile duct ligation in rats. Hepatol Res. (2002) 22(1):58–64.
   Google Scholar
• KAWABE T, CHEN ZS, WADA M et al: Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter (cMOAT/MRP2). FEBS Lett. (1999) 456(2):327–331.
   Google Scholar
• CUT Y, KONIG J, BUCHHOLZ JK et al.: Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. Mol. Pharmacol (1999) 55(5):929–937.
   Google Scholar
• BODO A, BAKOS E, SZERI F, VARADI A, SARKADI B: Differential modulation of the human liver conjugate transporters MRP2 and MRP3 by bile acids and organic anions. J. Biol. Chem. (2003) 278(26):23529–23537.
   Google Scholar
• KEPPLER D, CUT Y, KONIG J, LEIER I, NIES A: Export pumps for anionic conjugates encoded by MRP genes. Adv. Enzyme Regul. (1999) 39: 237–246.
   Google Scholar
• ISHIKAWA T, ALI-OSMAN F: Glutathione-associated cis-diamminedichloroplatinum(h) metabolism and ATP-dependent efflux from leukemia cells. Molecular characterization of glutathione-platinum complex and its biological significance. J. Biol Chem. (1993) 268(27):20116–20125.
   Google Scholar
• GUTMANN H, FRICKER G, DREWE J, TOEROEK M, MILLER DS: Interactions of HIV protease inhibitors with ATP-dependent drug export proteins. MoL Pharmacol. (1999) 56(2):383–389.
   Google Scholar
• MILLER DS: Nucleoside phosphonate interactions with multiple organic anion transporters in renal proximal tubule. Pharmacol Exp. Ther. (2001) 299(2):567–574.
   Google Scholar
• VAN AUBEL SMEETS PH, PETERS JG, BINDELS RJ, RUSSEL FG: The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J. Am. Soc. Nephrol (2002) 13(3):595–603.
   Google Scholar
• NARUHASHI K, TAMAI I, INOUE N et al.: Involvement of multidrug resistance-associated protein 2 in intestinal secretion of grepafloxacin in rats. Antimicrob. Agents Chemother. (2002) 46(2):344–349.
   Google Scholar
• MOTTINO AD, HOFFMAN T, JENNES L, VORE M: Expression and localization of multidrug resistant protein mrp2 in rat small intestine. J. PharmacoL Exp. Ther. (2000) 293(3):717–723.
   Google Scholar
• SCHWAB D, FISCHER H, TABATABAEI A, POLI S, HUWYLER J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J. Med. Chem. (2003) 46(9):1716–1725.
   Google Scholar
• SERRANO MA, MACIAS RI et al.: Expression of members of the multidrug resistance protein family in human term placenta. Am. J. Physiol Regul Integr. Comp. Physiol (2000) 279(4):R1495–R1503.
   Google Scholar
• SUZUKI H, SUGIYAMA Y: Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ ABCC2): its impact on drug disposition. Adv. Drug Deli v. Rev. (2002) 54(10):1311–1331.
   Google Scholar
• HINOSHITA E, UCHIUMI T, TAGUCHI K et al.: Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas. Clin. Cancer Res. (2000) 6(6):2401–2407.
   Google Scholar
• NIES AT, KONIG J, PFANNSCHMIDT M et al: Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma. Int. J. Cancer (2001) 94(4):492–499.
   Google Scholar
• STEINBACH D, LENGEMANN J, VOIGT A et al.: Response to chemotherapy and expression of the genes encoding the multidrug resistance-associated proteins MRP2, MRP3, MRP4, MRP5, and SMRP in childhood acute myeloid leukemia. Clin. Cancer Res. (2003) 9(3):1083–1086.
   Google Scholar
• BELINSKY MG, BAIN LJ, BALSARA BB, TESTA JR, KRUH GD: Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J. Natl Cancer Inst. (1998) 90(22):1735–1741.
   Google Scholar
• SCHEFFER GL, KOOL M, DE HAAS M et al: Tissue distribution and induction of human multidrug resistant protein 3. Lab. Invest. (2002) 82(2):193–201.
   Google Scholar
• KOOL M, VAN LINDEN M, DE HAAS M et al: MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc. Natl Acad. Sci. USA (1999) 96(12):6914–6919.
   Google Scholar
• KLEIN-SZANTO AJ, KRUH GD: Analysis of the MRP4 drug resistance profile in transfected NIH3T3 cells. J. Natl Cancer Inst. (2000) 92(23):1934–1940.
   Google Scholar
• MCALEER MA, BREEN MA, WHITE NL, MATTHEWS N: pABC11 (also known as MOAT-C and MRP5), a member of the ABC family of proteins, has anion transporter activity but does not confer multidrug resistance when overexpressed in human embryonic kidney 293 cells./ Biol. Chem. (1999) 274(33):23541–23548.
   Google Scholar
• CHEN ZS, KRUH GD: Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine. J. Biol. Chem. (2001) 276(36):33747–33754.
   Google Scholar
• NIES AT, SPRING H, THON WF, KEPPLER D, JEDLITSCHKY G: Immunolocalization of multidrug resistance protein 5 in the human genitourinary system. J. Urol. (2002) 167(5):2271–2275.
   Google Scholar
• BERA TK, LEE S, SALVATORE G, LEE B, PASTAN I: MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer. Mo/. Med. (2001) 7(8):509–516.
   Google Scholar
• TAMMUR J, PRADES C, ARNOULD I et al.: Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12. Gene (2001) 273(1):89–96.
   Google Scholar
• KOOL M, VAN LINDEN M, HAAS M, BAAS F, BORST P: Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells. Cancer Res. (1999) 59(1):175–182.
   Google Scholar
• HOPPER E, BELINSKY MG, ZENG H et al.: Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily. Cancer Lett. (2001) 162(2):181–191.
   Google Scholar
• LEGRAND O, SIMONIN G, BEAUCHAMP-NICOUD A, ZITTOUN R, MARIE JP: Simultaneous activity of MRP1 and Pgp is correlated with in vitro resistance to daunorubicin and with in vivo resistance in adult acute myeloid leukemia. Blood (1999) 94(3):1046–1056.
   Google Scholar
• LITMAN T, BRANGI M, HUDSON E et al.: The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J. Cell Sci. (2000) 113(Pt 11):2011–2021.
   Google Scholar
• BRUIN M, MIYAKE K, LITMAN T, ROBEY R, BATES SE: Reversal of resistance by GF120918 in cell lines expressing the ABC half-transporter, MXR. Cancer Lett. (1999) 146(2):117–126.
   Google Scholar
• ROCCHI E, KHODJAKOV A, VOLK EL et al.: The product of the ABC half-transporter gene ABCG2 (BCRP/MXRJ ABCP) is expressed in the plasma membrane. Biochem. Biophys. Res. Commun. (2000) 271(1):42–46.
   Google Scholar
• SCHEFFER GL, MALIEPAARD M, PIJNENBORG AC et al: Breast cancer resistance protein is localized at the plasma membrane in mitoxantrone- and topotecan-resistant cell lines. Cancer Res. (2000) 60(10):2589–2593.
   Google Scholar
• ••An excellent overview of enzymeinduction.
   Google Scholar
• DIESTRA JE, SCHEFFER GL, CATALA I et al.: Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material. J. Pathol (2002) 198(2):213–219.
   Google Scholar
• JONKER JW, SMIT JW, BRINKHUIS RF et al.: Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. j Natl. Cancer. Inst. (2000) 92(20):1651–1656.
   Google Scholar
• ELFERINK RO, GROEN AK: Genetic defects in hepatobiliary transport. Biochim. Biophys. Acta. (2002) 1586(2):129–145.
   Google Scholar
• FORD JM, HATT WN: Pharmacology of drugs that alter multidrug resistance in cancer. Pharmacol Rev. (1990) 42(3):155–199.
   Google Scholar
• FORD JM, HATT WN: Pharmacologic circumvention of multidrug resistance. Cytotechnology (1993) 12(1-3):171–212.
   Google Scholar
• KRISHNA R, MAYER LD: Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur. J. Pharm. Sci. (2000) 11(4):265–283.
   Google Scholar
• •This paper demonstrates classic examples of P-gp inhibitors strategies.
   Google Scholar
• WANG RB, KUO CL, LIEN LL, LIEN EJ: Structure-activity relationship: analyses of P-glycoprotein substrates and inhibitors. Clin. Pharm. Ther. (2003) 28(3):203–228.
   Google Scholar
• PIRKER R, FITZGERALD DJ, RASCHACK M et al: Enhancement of the activity of immunotoxins by analogues of verapamil. Cancer Res (1989) 49(17):4791–4795.
   Google Scholar
• PIRKER R, KEILHAUER G, RASCHACK M, LECHNER C, LUDWIG H: Reversal of multi-drug resistance in human KB cell lines by structural analogs of verapamil. Int. J. Cancer (1990) 45(5):916–919.
   Google Scholar
• TWENTYMAN PR: Modification of cytotoxic drug resistance by non-immuno-suppressive cyclosporins. Br. J. Cancer (1988) 57(3):254–258.
   Google Scholar
• ATADJA P, WATANABE T, XU H, COHEN D: PSC-833, a frontier in modulation of P-glycoprotein mediated multidrug resistance. Cancer Metastasis Rev. (1998) 17(2):163–168.
   Google Scholar
• NAWRATH H, RASCHACK M: Effects of (-)-desmethoxyverapamil on heart and vascular smooth muscle. J. Pharmacol. Exp. Ther. (1987) 242(3):1090–1097.
   Google Scholar
• KRISHNA R, MAYER LD: Liposomal doxorubicin circumvents PSC 833-free drug interactions, resulting in effective therapy of multidrug-resistant solid tumors. Cancer Res. (1997) 57(23):5246–5253.
   Google Scholar
• PIETRO A, CONSEIL G, PEREZ-VICTORIA JM et al: Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters. Cell Mot Lift Sci. (2002) 59(2):307–322.
   Google Scholar
• JODOIN J, DEMEULE M, BELIVEAU R: Inhibition of the multidrug resistance P-glycoprotein activity by green tea polyphenols. Biochim. Biophys. Acta. (2002) 1542(1-3):149–159.
   Google Scholar
• CVETKOVIC M, LEAKE B, FROMM MF, WILKINSON GR, KIM RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab. Dispos. (1999) 27(8):866–871.
   Google Scholar
• ARCECI RJ: Can multidrug resistance mechanisms be modified? Br. J. Haematol. (2000) 110(2):285–291.
   Google Scholar
• MINKO T, KOPECKOVA P, KOPECEK J: Chronic exposure to HPMA copolymer-bound adriamycin does not induce multidrug resistance in a human ovarian carcinoma cell line./ Control Release (1999) 59(2):133–148.
   Google Scholar
• TIJERINA M, FOWERS KD, KOPECKOVA P, KOPECEK J: Chronic exposure of human ovarian carcinoma cells to free or HPMA copolymer-bound mesochlorin e6 does not induce P-glycoprotein-mediated multidrug resistance. Biomaterials (2000) 21(21):2203–2210.
   Google Scholar
• ALAKHOV V, MOSKALEVA E, BATRAKOVA EV, KABANOV AV: Hypersensitization of multidrug resistant human ovarian carcinoma cells by pluronic P85 block copolymer. Bioconjug. Chem. (1996) 7(2):209–216.
   Google Scholar
• BATRAKOVA EV, LI S, ELMQUIST WF et al.: Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: Selective energy depletion. Br. J. Cancer. (2001) 85(12):1987–1997.
   Google Scholar
• MANO Y, SUZUKI H, TERASAKI T et al.: Kinetic analysis of the disposition of MRK16, an anti-P-glycoprotein monoclonal antibody, in tumors: comparison between in vitro and in vivo disposition. J. Pharmacol. Exp. Ther. (1997) 283(1):391–401.
   Google Scholar
• NAITO M, TSUGE H, KUROKO C et al.: Enhancement of cellular accumulation of cyclosporine by anti-P-glycoprotein monoclonal antibody MRK-16 and synergistic modulation of multidrug resistance. J. Natl Cancer Inst. (1993) 85(4):311–316.
   Google Scholar
• TANG F, BORCHARDT RT: Characterization of the efflux transporter(s) responsible for restricting intestinal mucosa permeation of the coumarinic acid-based cyclic prodrug of the opioid peptide DADLE. Pharm. Res. (2002) 19(6):787–793.
   Google Scholar
• GUILLEMARD V, SARAGOVI H: Prodrug chemotherapeutics bypass P-glycoprotein resistance and kill tumors in vivo with high efficacy and target-dependent selectivity. Oncogene (2004) 23(20):3613–3621.
   Google Scholar
• KABANOV AV, BATRAKOVA EV: New technologies for drug delivery across the blood brain barrier. Curr. Pharm. Des. (2004) 10(12):1355–1363.
   Google Scholar
• GRKOVIC S, BROWN MH, SKURRAY RA: Regulation of bacterial drug export systems. MicrobioL Mol. Biol. Rev. (2002) 66(4):671–701.
   Google Scholar
• GRKOVIC S, BROWN MH, SKURRAY RA: Transcriptional regulation of multidrug efflux pumps in bacteria. Semin. Cell Dev. Biol. (2001) 12(3):225–237.
   Google Scholar
• HINRICHS W, KISKER C, DUVEL M et al.: Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance. Science (1994) 264(5157):418–420.
   Google Scholar
• ORTH P, SCHNAPPINGER D, HILLEN W, SAENGER W, HINRICHS W: Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system. Nat. Struct. Biol. (2000) 7(3):215–219.
   Google Scholar
• HELDWEIN EE, BRENNAN RG: Crystal structure of the transcription activator BmrR bound to DNA and a drug. Nature (2001) 409(6818):378–382.
   Google Scholar
• SCHUMACHER MA, MILLER MC, GRKOVIC S et al.: Structural mechanisms of QacR induction and multidrug recognition. Science (2001) 294(5549):2158–2163.
   Google Scholar
• XU D, YE D, FISHER M, JULIANO RL: Selective inhibition of P-glycoprotein expression in multidrug-resistant tumor cells by a designed transcriptional regulator. Pharmacol Exp. Ther. (2002) 302(3):963–971.
   Google Scholar
• GALSKI H, SULLIVAN M, WILLINGHAM MC et al.: Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia. Mol Cell Biol. (1989) 9(104357–4363.
   Google Scholar
• HANANIA EG, FU S, ZU Z et ed.: Chemotherapy resistance to taxol in clonogenic progenitor cells following transduction of CD34 selected marrow and peripheral blood cells with a retrovirus that contains the MDR-1 chemotherapy resistance gene. Gene Ther. (1995) 2(4):285–294.
   Google Scholar
• SORRENTINO BP, BRANDT SJ, BODINE D et al.: Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR1. Science (1992) 257(5066):99–103.
   Google Scholar
• PODDA S, WARD M, HIMELSTEIN A et al.: Transfer and expression of the human multiple drug resistance gene into live mice. Proc. Natl Acad. Sci. USA (1992) 89(20):9676–9680.
   Google Scholar
• BACK DJ, ROGERS SM: Review: first-pass metabolism by the gastrointestinal mucosa. Aliment Pharmacol Ther. (1987) 1(5):339–357.
   Google Scholar
• GOMEZ DY, WACHER VJ, TOMLANOVICH SJ, HEBERT MF, BENET LZ: The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Clin. Pharmacol Ther. (1995) 58(1):15–19.
   Google Scholar
• KOLARS JC, AWNI WM, MERTON RM, WATKINS PB: First-pass metabolism of cyclosporin by the gut. Lancet (1991) 338(8781):1488–1490.
   Google Scholar
• PAINE MF, SHEN DD, KUNZE KL et al.: First-pass metabolism of midazolam by the human intestine. Clin. Pharmacol. Ther. (1996) 60(1):14–24.
   Google Scholar
• THUMMEL KE, O'SHEA D, PAINE MF et al.: Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin. Pharmacol Ther. (1996) 59(5):491–502.
   Google Scholar
• WEBBER IR, PETERS WH, BACK DJ: Cyclosporin metabolism by human gastrointestinal mucosal microsomes. Br. J. Clin. Pharmacol (1992) 33(6):661–664.
   Google Scholar
• TENNANT M, MCREE DE: The first structure of a microsomal P450-implications for drug discovery. Curr. Opin. Drug Discov. Devel (2001) 4(5):671–677.
   Google Scholar
• AHMAD N, MUKHTAR H: Cytochrome P450: a target for drug development for skin diseases. J. Invest Dermatol (2004) 123(3):417–425.
   Google Scholar
• GERVASINI G, CARRILLO JA, BENITEZ J: Potential role of cerebral cytochrome P450 in clinical pharmacokinetics: modulation by endogenous compounds. Clin. Pharmacokinet. (2004) 43(11):693–706.
   Google Scholar
• CHRISTIANS U: Transport proteins and intestinal metabolism: P-glycoprotein and cytochrome P4503A. Ther. Drug Monit. (2004) 26(2):104–106.
   Google Scholar
• AAAS Symposium on the Nature and Functional Role of Cytochrome P450 Mediated Systems. Houston, TX, USA. Drug Metab. Rev. (1979) 10(1):1–87.
   Google Scholar
• AHMAD S: The functional roles of cytochrome P450 mediated systems: present knowledge and future areas of investigations. Drug Metab. Rev. (1979) 10(1):1–14.
   Google Scholar
• MARSHALL WJ: Enzyme induction by drugs. Its relevance to clinical biochemistry. Ann. Clin. Biochem. (1978) 15(1):55–64.
   Google Scholar
• CHAMBAZ J, ROUSSET M: Intestinal responses to xenobiotics. Toxicol In Vitro (2001) 15(4-5):373–378.
   Google Scholar
• GUENGERICH FP: Uncommon P450-catalyzed reactions. Curr. Drug Metab. (2001) 2(2):93–115.
   Google Scholar
• SCHUETZ EG: Induction of cytochromes P450. Curr. Drug Metab. (2001) 2(2):139–147.
   Google Scholar
• ANZENBACHER P, ANZENBACHEROVA E: Cytochromes P450 and metabolism of xenobiotics. Cell Md. Lift Sci. (2001) 58(5-6):737–747.
   Google Scholar
• POL S, LEBRAY P: N-acetylcysteine for paracetamol poisoning: effect on prothrombin. Lancet (2002) 360(9340):1115.
   Google Scholar
• BROSEN K: Recent developments in hepatic drug oxidation. Implications for clinical pharmacokinetics. Clin. Pharmacokinet. (1990) 18(3):220–239.
   Google Scholar
• INGELMAN-SUNDBERG M: Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn Schmiedebergs Arch. Pharmacol (2004) 369(1):89–104.
   Google Scholar
• KELLY SL, LAMB DC, JACKSON CJ, WARRILOW AG, KELLY DE: The biodiversity of microbial cytochromes P450. Adv. Microb. Physiol (2003) 47:131–186.
   Google Scholar
• NEBERT DW, ADESNIK M, COON MJ et al.: The P450 gene superfamily: recommended nomenclature. DNA (1987) 6(1):1–11.
   Google Scholar
• SLAUGHTER RI,, EDWARDS DJ: Recent advances: the cytochrome P450 enzymes. Ann. Pharmacother. (1995) 29(6):619–624.
   Google Scholar
• DU L, HOFFMAN SM, KEENEY DS: Epidermal CYP2 family cytochromes P450. Toxicol Appl. Pharmacol (2004) 195(3):278–287.
   Google Scholar
• DING X, KAMINSKY LS: Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Ann. Rev. Pharmacol Toxicol (2003) 43:149–173.
   Google Scholar
• LIU M, HURN PD, ALKAYED NJ: Cytochrome P450 in neurological disease. Cuff. Drug Metab. (2004) 5(3):225–234.
   Google Scholar
• ZHAO X, IMIG JD: Kidney CYP450 enzymes: biological actions beyond drug metabolism. Curr. Drug Metab. (2003) 4(1):73–84.
   Google Scholar
• WATKINS PB, WRIGHTON SA, SCHUETZ EG, MOLOWA DT, GUZELIAN PS: Identification of glucocorticoid-inducible cytochromes P450 in the intestinal mucosa of rats and man. J. Clin. Invest. (1987) 80(4):1029–1036.
   Google Scholar
• SHEN DD, KUNZE KI,, THUMMEL KE: Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction. Adv. Drug Deliv. Rev. (1997) 27(2-3):99–127.
   Google Scholar
• KOLARS JC, SCHMIEDLIN-REN P, SCHUETZ JD, FANG C, WATKINS PB: Identification of rifampin-inducible P4501I1A4 (CYP3A4) in human small bowel enterocytes. J. Clin. Invest. (1992) 90(5):1871–1878.
   Google Scholar
• PARKINSON k An overview of current cytochrome P450 technology for assessing the safety and efficacy of new materials. lbxicol. PathoL (1996) 24(1):48–57.
   Google Scholar
• GUENGERICH FP, MARTIN MV BEAUNE PH et al.: Characterization of rat and human liver microsomal cytochrome P450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. J. Biol. Chem. (1986) 261(1 0:5051–5060.
   Google Scholar
• LOWN KS, KOLARS JC, THUMMEL KE et al.: Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test. Drug Metab. Dispos. (1994) 22(0:947–955.
   Google Scholar
• DING R, TAYROUZ Y, RIEDEL KD et al.: Substantial pharmacokinetic interaction between digoxin and ritonavir in healthy volunteers. Clin. Pharmacol. Ther. (2004) 76(0:73–84.
   Google Scholar
• SAGIR A, SCHMITT M, DILGER K, HAUSSINGER D: Inhibition of cytochrome P450 3A: relevant drug interactions in gastroenterology. Digestion (2003) 68(1):41–48.
   Google Scholar
• JIN L, CHEN IW, CHIBA M, LIN JH: Interaction with indinavir to enhance systemic exposure of an investigational HIV protease inhibitor in rats, dogs and monkeys. Xenobiotica (2003) 33(6):643–654.
   Google Scholar
• PFISTER M, LABBE L, LU JF et al.: Effect of coadministration of nelfinavir, indinavir, and saquinavir on the pharmacokinetics of amprenavir. Chn. Pharmacol Ther. (2002) 72(2):133–141.
   Google Scholar
• MALATY LI, KUPER JJ: Drug interactions of HIV protease inhibitors. Drug Sal' (1999) 20(2):147–169.
   Google Scholar
• ERESHEFSKY L, RIESENMAN C, LAM YW: Antidepressant drug interactions and the cytochrome P450 system. The role of cytochrome P450 2D6. CBn. Pharmacokinet. (1995) 29\(Supp1.1):10–18.
   Google Scholar
• HIEMKE C, HARTTER S: Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol. Ther. (2000) 85(1):11–28.
   Google Scholar
• MOLTKE LL, GREENBLATT DJ, SCHMIDER J, HARMATZ JS, SHADER RI: Metabolism of drugs by cytochrome P450 3A isoforms. Implications for drug interactions in psychopharmacology. CBn. Pharmacokinet. (1995) 29\(Supp1.1):33–43.
   Google Scholar
• MOLTKE LL, GREENBLATT DJ, SCHMIDER J et al.: Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J. CBn. Pharmacol (1996) 36(9):783–791.
   Google Scholar
• GREGOR KJ, WAY K, YOUNG CH, JAMES SP: Concomitant use of selective serotonin reuptake inhibitors with other cytochrome P450 2D6 or 3A4 metabolized medications: how often does it really happen?J. Affect. Disord. (1997) 46(1):59–67.
   Google Scholar
• OZMINKOWSKI RJ, HYLAN TR, MELFI CA et al.: Economic consequences of selective serotonin reuptake inhibitor use with drugs also metabolized by the cytochrome P450 system. CBn. Ther. (1998) 20(4):780–796.
   Google Scholar
• VELLA S, FLORIDIA M: Saquinavir. Clinical pharmacology and efficacy. Clin. Pharmacokinet. (1998) 34(3):189–201.
   Google Scholar
• HSU A, GRANNEMAN GR, BERTZ RJ: Ritonavir. Clinical pharmacokinetics and interactions with other anti-HIV agents. Clin. Pharmacokinet. (1998) 35(4):275–291.
   Google Scholar
• WILLIAMS GC, SINKO PJ: Oral absorption of the HIV protease inhibitors: a current update. Adv. Drug Deliv. Rev. (1999) 39(1-3):211–238.
   Google Scholar
• LI X, CT-JAN WK: Transport, metabolism and elimination mechanisms of anti-HIV agents. Adv. Drug Deliv. Rev. (1999) 39(1-3):81–103.
   Google Scholar
• BLACK DJ, KUNZE KL, WIENKERS LC et al.: Warfarin-fluconazole. II. A metabolically based drug interaction: in vivo studies. Drug Metab. Dispos. (1996) 24(4):422–428.
   Google Scholar
• KUNZE KL, WIENKERS LC, THUMMEL KE, TRAGER WF: Warfarin-fluconazole. I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. Drug Metab. Dispos. (1996) 24(4):414–421.
   Google Scholar
• HARDER S, THURMANN P: Clinically important drug interactions with anticoagulants. An update. Clin. Pharmacokinet. (1996) 30(6):416–444.
   Google Scholar
• ZHOU S, CHAN E, PAN SQ, HUANG M, LEE EJ: Pharmacokinetic interactions of drugs with St John's wort. J. PsychopharmacoL (2004) 18(2):262–276.
   Google Scholar
• OUELLET D, HSU A, QIAN J et al.: Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. Br. J. Clin. Pharmacol. (1998) 46(2):111–116.
   Google Scholar
• MOYLE GJ, BACK D: Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIT/Med. (2001) 2(2):105–113.
   Google Scholar
• QAZI NA, MORLESE JF, POZNIAK AL: Lopinavir/ritonavir (ABT-378/r). Expert Opin. Pharmacother. (2002) 3(3):315–327.
   Google Scholar
• MOYLE G: Overcoming obstacles to the success of protease inhibitors in highly active antiretroviral therapy regimens. AIDS Patient Care STDS (2002) 16(12):585–597.
   Google Scholar
• BERGSHOEFF AS, WOLFS TF, GEELEN SP, BURGER DM: Ritonavir-enhanced pharmacokinetics of nelfinavir/ M8 during rifampin use. Ann. Pharmacother. (2003) 37(4):521–525.
   Google Scholar
• JOHNSON M, PETERS B: Saquinavir/ low-dose ritonavir: its use in HIV infection. AIDS Rev. (2003) 5(1):44–51.
   Google Scholar
• LOUTFY M, RABOUD J, THOMPSON C et al.: Clinical impact of double protease inhibitor boosting with lopinavir/ritonavir and amprenavir as part of salvage antiretroviral therapy. HIV Clin. Trials (2003) 4(5):301–310.
   Google Scholar
• ARORA V, GATE ML, GHOSH C, IVERSEN PL: Phosphorodiamidate morpholino antisense oligomers inhibit expression of human cytochrome P450 3A4 and alter selected drug metabolism. Drug Metab. Dispos. (2002) 30(7):757–762.
   Google Scholar
• •A classic demonstration of anti-sense strategy to inhibit GYP.
   Google Scholar
• JOVER R, BORT R, GOMEZ-LECHON MJ, CASTELL JV: Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: a study using adenovirus-mediated antisense targeting. Hepato/ogy (2001) 33(3):668–675.
   Google Scholar
• ARORA V, KNAPP DC, REDDY MT, WELLER DD, IVERSEN PL: Bioavailability and efficacy of antisense morpholino oligomers targeted to c-myc and cytochrome P450 3A2 following oral administration in rats. J. Pharm. Sci. (2002) 91(4):1009–1018.
   Google Scholar
• ARORA V, HANNAH TL, IVERSEN PL, BRAND RM: Transdermal use of phosphorodiamidate morpholino oligomer AVI-4472 inhibits cytochrome P450 3A2 activity in male rats. Pharm. Res. (2002) 19(10):1465–1470.
   Google Scholar
• ARORA V, IVERSEN PL: Redirection of drug metabolism using antisense technology. Curr. Opin. MoL Ther. (2001) 3(3):249–257.
   Google Scholar
• KATOH M, NAKAJIMA M, YAMAZAKI H, YOKOI T: Inhibitory effects of CYP3A4 substrates and their metabolites on P- glycoprotein-mediated transport. Eur. j Pharm. Sci. (2001) 12(4):505–513.
   Google Scholar
• KOLARS JC, STETSON PL, RUSH BD et al: Cyclosporine metabolism by P450IIIA in rat enterocytes-another determinant of oral bioavailability? Transplantation (1992) 53(3):596–602.
   Google Scholar
• CHIOU WL, CHUNG SM, WU TC: Potential role of P-glycoprotein in affecting hepatic metabolism of drugs. Pharm. Res. (2000) 17(8):903–905.
   Google Scholar
• WACHER VJ, SALPHATI L, BENET LZ: Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv. Drug Deliv. Rev. (2001) 46(1-3):89–102.
   Google Scholar
• ••An excellent overview of efflux pumps andmetabolic enzymes.
   Google Scholar
• WATKINS PB: The barrier function of CYP3A4 and P-glycoprotein in the small bowel. Adv. Drug. Deliv. Rev. (1997) 27(2-3):161–170.
   Google Scholar
• MITRA AK, PATEL J: Strategies to overcome simultaneous P-glycoprotein mediated efflux and CYP3A4 mediated metabolism of drugs. Pharmacogenomics (2001) 2(4):401–415.
   Google Scholar
• ••An excellent overview of efflux pumps andmetabolic enzymes.
   Google Scholar
• MEYER UA: Pharmacogenetics - five decades of therapeutic lessons from genetic diversity. Nat. Rev. Genet (2004) 5(9):669–676.
   Google Scholar
• ANGLICHEAU D, LEGENDRE C, THERVET E: Pharmacogenetics in solid organ transplantation: present knowledge and future perspectives. Transplantation (2004) 78(3):311–315.
   Google Scholar
• SENN S: Individual response to treatment: is it a valid assumption? BMJ (2004) 329(7472):966–968.
   Google Scholar
• ISHIKAWA T, HIRANO H, ONISHI Y, SAKURAI A. TARUI S: Functional evaluation of ABCB1 (P-glycoprotein) polymorphisms: high-speed screening and structure-activity relationship analyses. Drug Metab. Pharmacokinet. (2004) 19(1):1–14.
   Google Scholar
• MEALEY KL: Therapeutic implications of the MDR-1 gene./ Vet. Pharmacol. Ther. (2004) 27(5):257–264.
   Google Scholar
• ISHIKAWA T, ONISHI Y, HIRANO H et al.: Pharmacogenomics of drug transporters: a new approach to functional analysis of the genetic polymorphisms of ABCB1 (P-glycoprotein/MDR1). Biol. Pharm. Bull (2004) 27(7):939–948.
   Google Scholar
• EICHELBAUM M, FROMM MF, SCHWAB M: Clinical aspects of the MDR1 (ABCB1) gene polymorphism. Ther. Drug Monit. (2004) 26(2):180–185.
   Google Scholar
• IEIRI I, TAKANE H, OTSUBO K: The MDR1 (ABCB1) gene polymorphism and its clinical implications. Clin. Pharmacokinet. (2004) 43(9):553–576.
   Google Scholar
• JAMROZIAK K, ROBAK T: Pharmacogenomics of MDR1/ABCB1 gene: the influence on risk and clinical outcome of haematological malignancies. Hematology (2004) 9(2):91–105.
   Google Scholar
• LIN JH, LU AY: Interindividual variability in inhibition and induction of cytochrome P450 enzymes. Ann. Rev. Pharmacol. ToxicoL (2001) 41:535–567.
   Google Scholar
• GARCIA-MARTIN E, MARTINEZ C, PIZARRO RM et al.: CYP3A4 variant alleles in white individuals with low CYP3A4 enzyme activity. Clin. Pharmacol. Ther. (2002) 71(3):196–204.
   Google Scholar
• CHANG GWM, KAM PC: The physiological and pharmacological roles of cytochrome P450 isoenzymes. Anaesthesia (1999) 54(1):42–50.
   Google Scholar
• SYNOLD TW, DUSSAULT I, FORMAN BM: The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat. Med. (2001) 7(5):584–590.
   Google Scholar
• GEICK A, EICHELBAUM M, BURK 0: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J. Biol. Chem. (2001) 276(18):14581–14587.
   Google Scholar
• QUATTROCHI LC, GUZELIAN PS: Cyp3A regulation: from pharmacology to nuclear receptors. Drug Metab. Dispos. (2001) 29(5):615–622.
   Google Scholar
• JONES SA, MOORE LB, SHENK JL et al.: The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. MoL EndocrinoL (2000) 14(1):27–39.
   Google Scholar
• ••An excellent review on nuclear receptors.
   Google Scholar
• MASUYAMA H, HIRAMATSU Y, MIZUTANI Y, INOSHITA H, KUDO T: The expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in perinatal mouse. MoL Cell Endocrinol. (2001) 172(1-2):47–56.
   Google Scholar
• CATANIA VA, POZZI EJ, LUQUITA MG et al.: Co-regulation of expression of Phase II metabolizing enzymes and multidrug resistance-associated protein 2. Ann. Hipatol. (2004) 3(1):11–17.
   Google Scholar
• DICKINS M: Induction of cytochromes P450. Curr. Top Med. Chem. (2004) 4(16):1745–1766.
   Google Scholar
• ELORANTA JJ, KULLAK-UBLICK GA: Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch. Biochem. Biophys. (2005) 433(2):397–412.
   Google Scholar
• GOODWIN B, MOORE JT: CAR: detailing new models. Trends Pharmacol Sci. (2004) 25(8):437–441.
   Google Scholar
• HANDSCHIN C, MEYER UA: Induction of drug metabolism: the role of nuclear receptors. Pharmacol Rev. (2003) 55(0649–673.
   Google Scholar
• HANDSCHIN C, MEYER UA: Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Arch. Biochem. Biophys. (2005) 433(2):387–396.
   Google Scholar
• KULLAK-UBLICK GA, BECKER MB: Regulation of drug and bile salt transporters in liver and intestine. Drug Metab. Rev. (2003) 35(4):305–317.
   Google Scholar
• MANNEL M: Drug interactions with St John's wort: mechanisms and clinical implications. Drug Sal: (2004) 27(11):773–797.
   Google Scholar
• MOHAN R, HEYMAN RA: Orphan nuclear receptor modulators. Cuff. Thp Med. Chem. (2003) 3(14):1637–1647.
   Google Scholar
• MULLER M: Transcriptional control of hepatocanalicular transporter gene expression. Semin. Liver Dis. (2000) 20(3):323–337.
   Google Scholar
• TRABER MG: Vitamin E, nuclear receptors and xenobiotic metabolism. Arch. Biochem. Biophys. (2004) 423(1):6–11.
   Google Scholar
• WANG H, LECLUYSE EL: Role of orphan nuclear receptors in the regulation of drug-metabolising enzymes. Clin. Pharmacokinet. (2003) 42(15):1331–1357.
   Google Scholar
• YOU L: Steroid hormone biotransformation and xenobiotic induction of hepatic steroid metabolizing enzymes. Chem. Biol. Interact. (2004) 147(3):233–246.
   Google Scholar
• TANG-WAI DF, BROSSI A, ARNOLD LD, GROS P: The nitrogen of the acetamido group of colchicine modulates P-glycoprotein-mediated multidrug resistance. Biochemistry (1993) 32(25):6470–6476.
   Google Scholar
• MICHAELIS ML, GEORG G et al.: Overcoming the blood-brain barrier to taxane delivery for neurodegenerative diseases and brain tumors. J. MoL Neurosci. (2003) 20(3):339–343.
   Google Scholar
• WENDER PA, HEGDE SG, HUBBARD RD, ZHANG L, MOOBERRY SL: Synthesis and biological evaluation of H-laulimalide analogues. Org Lett. (2003) 5(19):3507–3509.
   Google Scholar