Relevance of ABC Transporters in Drug Development

Page: [434 - 446] Pages: 13

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Abstract

ATP-binding cassette (ABC) transporters play a critical role in protecting vital organs such as the brain and placenta against xenobiotics, as well as in modulating the pharmacological and toxicological profile of several drug candidates by restricting their penetration through cellular and tissue barriers. This review paper describes the structure and function of ABC transporters as well as the role of P-glycoprotein, multidrug resistance-associated protein 2 and breast cancer resistance protein in the disposition of drugs. Furthermore, a review of the in vitro and in vivo techniques for evaluating the interaction between drugs and ABC transporters is provided.

Keywords: P-glycoprotein, multidrug resistance-associated protein 2, breast cancer resistance protein, drug development, pharmacokinetics, pharmacodynamics.

Graphical Abstract

[1]
Nwabufo, C.; Krol, E. Unraveling the metabolic fate of potential therapeutic dimer compounds for Parkinson’s disease. Drug Metab. Pharmacokinet., 2019, 34, S59-S60.
[http://dx.doi.org/10.1016/j.dmpk.2018.09.208]
[2]
Nwabufo, C.K. Introduction to the mini special issue on next generation drug discovery and development: Rethinking translational pharma-cology for accelerated drug development. Drug Metab. Rev., 2021, 53(2), 171-172.
[http://dx.doi.org/10.1080/03602532.2021.1909614] [PMID: 33962522]
[3]
Nwabufo, C.K.; Aigbogun, O.P.; Allen, K.J.H.; Owens, M.N.; Lee, J.S.; Phenix, C.P.; Krol, E.S. Employing in vitro metabolism to guide de-sign of F-labelled PET probes of novel α-synuclein binding bifunctional compounds. Xenobiotica, 2021, 51(8), 885-900.
[http://dx.doi.org/10.1080/00498254.2021.1943566] [PMID: 34187286]
[4]
Nwabufo, C.K.; El-Aneed, A.; Krol, E.S. Tandem mass spectrometric analysis of novel caffeine scaffold-based bifunctional compounds for Parkinson’s disease. Rapid Commun. Mass Spectrom., 2019, 33(23), 1792-1803.
[http://dx.doi.org/10.1002/rcm.8540] [PMID: 31351020]
[5]
Knights, K.M.; Stresser, D.M.; Miners, J.O.; Crespi, C.L. In vitro drug metabolism using liver microsomes. Curr. Protoc. Pharmacol., 2016. 74, 7.8.1-7.8.24.
[6]
Stanley, L.A. Drug metabolism. In: Badal, S.; Delgoda, R.; Eds.Pharmacognosy: Fundamentals, Applications and Strategies; Academic Press: Cambridge, Massachusetts, 2017, pp. 527-545.
[7]
Döring, B.; Petzinger, E. Phase 0 and phase III transport in various organs: Combined concept of phases in xenobiotic transport and metabo-lism. Drug Metab. Rev., 2014, 46(3), 261-282.
[http://dx.doi.org/10.3109/03602532.2014.882353] [PMID: 24483608]
[8]
Hagenbuch, B.; Meier, P.J. Organic anion transporting polypeptides of the OATP/SLC21 family: Phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch., 2004, 447(5), 653-665.
[http://dx.doi.org/10.1007/s00424-003-1168-y] [PMID: 14579113]
[9]
Koepsell, H.; Endou, H. The SLC22 drug transporter family. Pflugers Arch., 2004, 447(5), 666-676.
[http://dx.doi.org/10.1007/s00424-003-1089-9] [PMID: 12883891]
[10]
Ayrton, A.; Morgan, P. Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica, 2001, 31(8-9), 469-497.
[http://dx.doi.org/10.1080/00498250110060969] [PMID: 11569523]
[11]
Borst, P.; Elferink, R.O. Mammalian ABC transporters in health and disease. Annu. Rev. Biochem., 2002, 71, 537-592.
[http://dx.doi.org/10.1146/annurev.biochem.71.102301.093055] [PMID: 12045106]
[12]
Fromm, M.F. P-glycoprotein: A defense mechanism limiting oral bioavailability and CNS accumulation of drugs. Int. J. Clin. Pharmacol. Ther., 2000, 38(2), 69-74.
[http://dx.doi.org/10.5414/CPP38069] [PMID: 10706193]
[13]
Fromm, M.F. Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol. Sci., 2004, 25(8), 423-429.
[http://dx.doi.org/10.1016/j.tips.2004.06.002] [PMID: 15276711]
[14]
Schinkel, A.H.; Jonker, J.W. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: An overview. Adv. Drug Deliv. Rev., 2003, 55(1), 3-29.
[http://dx.doi.org/10.1016/S0169-409X(02)00169-2] [PMID: 12535572]
[15]
Jones, P.M.; George, A.M. The ABC transporter structure and mechanism: Perspectives on recent research. Cell. Mol. Life Sci., 2004, 61(6), 682-699.
[http://dx.doi.org/10.1007/s00018-003-3336-9] [PMID: 15052411]
[16]
Glavinas, H.; Krajcsi, P.; Cserepes, J.; Sarkadi, B. The role of ABC transporters in drug resistance, metabolism and toxicity. Curr. Drug Deliv., 2004, 1(1), 27-42.
[http://dx.doi.org/10.2174/1567201043480036] [PMID: 16305368]
[17]
Rosenberg, M.F.; Kamis, A.B.; Callaghan, R.; Higgins, C.F.; Ford, R.C. Three-dimensional structures of the mammalian multidrug resistance P-glycoprotein demonstrate major conformational changes in the transmembrane domains upon nucleotide binding. J. Biol. Chem., 2003, 278(10), 8294-8299.
[http://dx.doi.org/10.1074/jbc.M211758200] [PMID: 12501241]
[18]
Szakács, G.; Váradi, A.; Ozvegy-Laczka, C.; Sarkadi, B. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discov. Today, 2008, 13(9-10), 379-393.
[http://dx.doi.org/10.1016/j.drudis.2007.12.010] [PMID: 18468555]
[19]
Giacomini, K.M.; Huang, S-M.; Tweedie, D.J.; Benet, L.Z.; Brouwer, K.L.R.; Chu, X.; Dahlin, A.; Evers, R.; Fischer, V.; Hillgren, K.M.; Hoffmaster, K.A.; Ishikawa, T.; Keppler, D.; Kim, R.B.; Lee, C.A.; Niemi, M.; Polli, J.W.; Sugiyama, Y.; Swaan, P.W.; Ware, J.A.; Wright, S.H.; Yee, S.W.; Zamek-Gliszczynski, M.J.; Zhang, L. Membrane transporters in drug development. Nat. Rev. Drug Discov., 2010, 9(3), 215-236.
[http://dx.doi.org/10.1038/nrd3028] [PMID: 20190787]
[20]
Bleasby, K.; Castle, J.C.; Roberts, C.J.; Cheng, C.; Bailey, W.J.; Sina, J.F.; Kulkarni, A.V.; Hafey, M.J.; Evers, R.; Johnson, J.M.; Ulrich, R.G.; Slatter, J.G. Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: A resource for investigations into drug disposition. Xenobiotica, 2006, 36(10-11), 963-988.
[http://dx.doi.org/10.1080/00498250600861751] [PMID: 17118916]
[21]
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(9), 1277-1287.
[http://dx.doi.org/10.1177/38.9.1974900] [PMID: 1974900]
[22]
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(21), 7735-7738.
[http://dx.doi.org/10.1073/pnas.84.21.7735] [PMID: 2444983]
[23]
Seelig, A.; Landwojtowicz, E. Structure-activity relationship of P-glycoprotein substrates and modifiers. Eur. J. Pharm. Sci., 2000, 12(1), 31-40.
[http://dx.doi.org/10.1016/S0928-0987(00)00177-9] [PMID: 11121731]
[24]
Litman, T.; Skovsgaard, T.; Stein, W.D. Pumping of drugs by P-glycoprotein: A two-step process? J. Pharmacol. Exp. Ther., 2003, 307(3), 846-853.
[http://dx.doi.org/10.1124/jpet.103.056960] [PMID: 14534356]
[25]
Loo, T.W.; Bartlett, M.C.; Clarke, D.M. Substrate-induced conformational changes in the transmembrane segments of human P-glycoprotein. Direct evidence for the substrate-induced fit mechanism for drug binding. J. Biol. Chem., 2003, 278(16), 13603-13606.
[http://dx.doi.org/10.1074/jbc.C300073200] [PMID: 12609990]
[26]
Pawagi, A.B.; Wang, J.; Silverman, M.; Reithmeier, R.A.; Deber, C.M. Transmembrane aromatic amino acid distribution in P-glycoprotein. A functional role in broad substrate specificity. J. Mol. Biol., 1994, 235(2), 554-564.
[http://dx.doi.org/10.1006/jmbi.1994.1013] [PMID: 7904655]
[27]
Chinn, L.W.; Kroetz, D.L. ABCB1 pharmacogenetics: Progress, pitfalls, and promise. Clin. Pharmacol. Ther., 2007, 81(2), 265-269.
[http://dx.doi.org/10.1038/sj.clpt.6100052] [PMID: 17259950]
[28]
Choudhuri, S.; Klaassen, C.D. Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters. Int. J. Toxicol., 2006, 25(4), 231-259.
[http://dx.doi.org/10.1080/10915810600746023] [PMID: 16815813]
[29]
Kimura, Y.; Morita, S.Y.; Matsuo, M.; Ueda, K. Mechanism of multidrug recognition by MDR1/ABCB1. Cancer Sci., 2007, 98(9), 1303-1310.
[http://dx.doi.org/10.1111/j.1349-7006.2007.00538.x] [PMID: 17608770]
[30]
Miller, D.S.; Bauer, B.; Hartz, A.M.S. Modulation of P-glycoprotein at the blood-brain barrier: Opportunities to improve central nervous system pharmacotherapy. Pharmacol. Rev., 2008, 60(2), 196-209.
[http://dx.doi.org/10.1124/pr.107.07109] [PMID: 18560012]
[31]
Raub, T.J. P-glycoprotein recognition of substrates and circumvention through rational drug design. Mol. Pharm., 2006, 3(1), 3-25.
[http://dx.doi.org/10.1021/mp0500871] [PMID: 16686365]
[32]
Zhou, S.F. Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica, 2008, 38(7-8), 802-832.
[http://dx.doi.org/10.1080/00498250701867889] [PMID: 18668431]
[33]
Ni, Z.; Mao, Q. ATP-binding cassette efflux transporters in human placenta. Curr. Pharm. Biotechnol., 2011, 12(4), 674-685.
[http://dx.doi.org/10.2174/138920111795164057] [PMID: 21118087]
[34]
Vähäkangas, K.; Myllynen, P. Drug transporters in the human blood-placental barrier. Br. J. Pharmacol., 2009, 158(3), 665-678.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00336.x] [PMID: 19788499]
[35]
del Moral, R.G.; Olmo, A.; Aguilar, M.; O’Valle, F. P glycoprotein: A new mechanism to control drug-induced nephrotoxicity. Exp. Nephrol., 1998, 6(2), 89-97.
[http://dx.doi.org/10.1159/000020510] [PMID: 9567214]
[36]
Schinkel, A.H.; Smit, J.J.; van Tellingen, O.; Beijnen, J.H.; Wagenaar, E.; van Deemter, L.; Mol, C.A.; van der Valk, M.A.; Robanus-Maandag, E.C.; te Riele, H.P. Disruption of the mouse MDR1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to in-creased sensitivity to drugs. Cell, 1994, 77(4), 491-502.
[http://dx.doi.org/10.1016/0092-8674(94)90212-7] [PMID: 7910522]
[37]
Paul, A.J.; Tranquilli, W.J.; Seward, R.L.; Todd, K.S., Jr; DiPietro, J.A. Clinical observations in collies given ivermectin orally. Am. J. Vet. Res., 1987, 48(4), 684-685.
[PMID: 3592367]
[38]
Pulliam, J.D.; Seward, R.L.; Henry, R.T.; Steinberg, S.A. Investigating ivermectin toxicity in collies. Vet Med-Us, 1985, 80(6), 33.
[39]
Seward, R.L. Reactions in dogs given ivermectin. J. Am. Vet. Med. Assoc., 1983, 183(5), 493-493.
[PMID: 6688617]
[40]
Tranquilli, W.J.; Paul, A.J.; Seward, R.L. Ivermectin plasma concentrations in collies sensitive to ivermectin-induced toxicosis. Am. J. Vet. Res., 1989, 50(5), 769-770.
[PMID: 2729723]
[41]
Mealey, K.L.; Bentjen, S.A.; Gay, J.M.; Cantor, G.H. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics, 2001, 11(8), 727-733.
[http://dx.doi.org/10.1097/00008571-200111000-00012] [PMID: 11692082]
[42]
Roulet, A.; Puel, O.; Gesta, S.; Lepage, J.F.; Drag, M.; Soll, M.; Alvinerie, M.; Pineau, T. MDR1-deficient genotype in Collie dogs hypersen-sitive to the P-glycoprotein substrate ivermectin. Eur. J. Pharmacol., 2003, 460(2-3), 85-91.
[http://dx.doi.org/10.1016/S0014-2999(02)02955-2] [PMID: 12559367]
[43]
Katragadda, S.; Budda, B.; Anand, B.S.; Mitra, A.K. Role of efflux pumps and metabolising enzymes in drug delivery. Expert Opin. Drug Deliv., 2005, 2(4), 683-705.
[http://dx.doi.org/10.1517/17425247.2.4.683] [PMID: 16296794]
[44]
Löscher, W.; Luna-Tortós, C.; Römermann, K.; Fedrowitz, M. Do ATP-binding cassette transporters cause pharmacoresistance in epilepsy? Problems and approaches in determining which antiepileptic drugs are affected. Curr. Pharm. Des., 2011, 17(26), 2808-2828.
[http://dx.doi.org/10.2174/138161211797440212] [PMID: 21827408]
[45]
Zhou, S.F.; Lai, X. An update on clinical drug interactions with the herbal antidepressant St. John’s wort. Curr. Drug Metab., 2008, 9(5), 394-409.
[http://dx.doi.org/10.2174/138920008784746391] [PMID: 18537576]
[46]
Patel, N.H.; Rothenberg, M.L. Multidrug resistance in cancer chemotherapy. Invest. New Drugs, 1994, 12(1), 1-13.
[http://dx.doi.org/10.1007/BF00873229] [PMID: 7960599]
[47]
Binkhathlan, Z.; Lavasanifar, A. P-glycoprotein inhibition as a therapeutic approach for overcoming multidrug resistance in cancer: Current status and future perspectives. Curr. Cancer Drug Targets, 2013, 13(3), 326-346.
[http://dx.doi.org/10.2174/15680096113139990076] [PMID: 23369096]
[48]
Breier, A.; Gibalova, L.; Seres, M.; Barancik, M.; Sulova, Z. New insight into p-glycoprotein as a drug target. Anticancer. Agents Med. Chem., 2013, 13(1), 159-170.
[http://dx.doi.org/10.2174/187152013804487380] [PMID: 22931413]
[49]
Nobili, S.; Landini, I.; Mazzei, T.; Mini, E. Overcoming tumor multidrug resistance using drugs able to evade P-glycoprotein or to exploit its expression. Med. Res. Rev., 2012, 32(6), 1220-1262.
[http://dx.doi.org/10.1002/med.20239] [PMID: 21374643]
[50]
Wakabayashi, K.; Tamura, A.; Saito, H.; Onishi, Y.; Ishikawa, T. Human ABC transporter ABCG2 in xenobiotic protection and redox biolo-gy. Drug Metab. Rev., 2006, 38(3), 371-391.
[http://dx.doi.org/10.1080/03602530600727947] [PMID: 16877258]
[51]
Doyle, L.A.; Yang, W.; Abruzzo, L.V.; Krogmann, T.; Gao, Y.; Rishi, A.K.; Ross, D.D. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl. Acad. Sci. USA, 1998, 95(26), 15665-15670.
[http://dx.doi.org/10.1073/pnas.95.26.15665] [PMID: 9861027]
[52]
Robey, R.W.; To, K.K.; Polgar, O.; Dohse, M.; Fetsch, P.; Dean, M.; Bates, S.E. ABCG2: A perspective. Adv. Drug Deliv. Rev., 2009, 61(1), 3-13.
[http://dx.doi.org/10.1016/j.addr.2008.11.003] [PMID: 19135109]
[53]
Eisenblätter, T.; Hüwel, S.; Galla, H.J. Characterisation of the brain multidrug resistance protein (BMDP/ABCG2/BCRP) expressed at the blood-brain barrier. Brain Res., 2003, 971(2), 221-231.
[http://dx.doi.org/10.1016/S0006-8993(03)02401-6] [PMID: 12706238]
[54]
Fetsch, P.A.; Abati, A.; Litman, T.; Morisaki, K.; Honjo, Y.; Mittal, K.; Bates, S.E. Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues. Cancer Lett., 2006, 235(1), 84-92.
[http://dx.doi.org/10.1016/j.canlet.2005.04.024] [PMID: 15990223]
[55]
Huls, M.; Brown, C.D.A.; Windass, A.S.; Sayer, R.; van den Heuvel, J.J.M.W.; Heemskerk, S.; Russel, F.G.M.; Masereeuw, R. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane. Kidney Int., 2008, 73(2), 220-225.
[http://dx.doi.org/10.1038/sj.ki.5002645] [PMID: 17978814]
[56]
Maliepaard, M.; Scheffer, G.L.; Faneyte, I.F.; van Gastelen, M.A.; Pijnenborg, A.C.; Schinkel, A.H.; van De Vijver, M.J.; Scheper, R.J.; Schellens, J.H. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res., 2001, 61(8), 3458-3464.
[PMID: 11309308]
[57]
van Herwaarden, A.E.; Schinkel, A.H. The function of breast cancer resistance protein in epithelial barriers, stem cells and milk secretion of drugs and xenotoxins. Trends Pharmacol. Sci., 2006, 27(1), 10-16.
[http://dx.doi.org/10.1016/j.tips.2005.11.007] [PMID: 16337280]
[58]
Vlaming, M.L.; Lagas, J.S.; Schinkel, A.H. Physiological and pharmacological roles of ABCG2 (BCRP): Recent findings in ABCG2 knockout mice. Adv. Drug Deliv. Rev., 2009, 61(1), 14-25.
[http://dx.doi.org/10.1016/j.addr.2008.08.007] [PMID: 19118589]
[59]
Litman, T.; Brangi, M.; Hudson, E.; Fetsch, P.; Abati, A.; Ross, D.D.; Miyake, K.; Resau, J.H.; Bates, S.E. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J. Cell Sci., 2000, 113(Pt 11), 2011-2021.
[http://dx.doi.org/10.1242/jcs.113.11.2011] [PMID: 10806112]
[60]
Kruijtzer, C.M.; Beijnen, J.H.; Rosing, H.; ten Bokkel Huinink, W.W.; Schot, M.; Jewell, R.C.; Paul, E.M.; Schellens, J.H. Increased oral bio-availability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J. Clin. Oncol., 2002, 20(13), 2943-2950.
[http://dx.doi.org/10.1200/JCO.2002.12.116] [PMID: 12089223]
[61]
Kuppens, I.E.; Witteveen, E.O.; Jewell, R.C.; Radema, S.A.; Paul, E.M.; Mangum, S.G.; Beijnen, J.H.; Voest, E.E.; Schellens, J.H. A phase I, randomized, open-label, parallel-cohort, dose-finding study of elacridar (GF120918) and oral topotecan in cancer patients. Clin. Cancer Res., 2007, 13(11), 3276-3285.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2414] [PMID: 17545533]
[62]
Furman, W.L.; Navid, F.; Daw, N.C.; McCarville, M.B.; McGregor, L.M.; Spunt, S.L.; Rodriguez-Galindo, C.; Panetta, J.C.; Crews, K.R.; Wu, J.; Gajjar, A.J.; Houghton, P.J.; Santana, V.M.; Stewart, C.F. Tyrosine kinase inhibitor enhances the bioavailability of oral irinotecan in pedi-atric patients with refractory solid tumors. J. Clin. Oncol., 2009, 27(27), 4599-4604.
[http://dx.doi.org/10.1200/JCO.2008.19.6642] [PMID: 19687340]
[63]
Mao, Q.; Unadkat, J.D. Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J., 2005, 7(1), E118-E133.
[http://dx.doi.org/10.1208/aapsj070112] [PMID: 16146333]
[64]
Meyer zu Schwabedissen, H.E.; Kroemer, H.K. In vitro and in vivo evidence for the importance of breast cancer resistance protein transport-ers (BCRP/MXR/ABCP/ABCG2). Handb. Exp. Pharmacol., 2011, (201), 325-371.
[http://dx.doi.org/10.1007/978-3-642-14541-4_9] [PMID: 21103975]
[65]
Kruh, G.D.; Belinsky, M.G. The MRP family of drug efflux pumps. Oncogene, 2003, 22(47), 7537-7552.
[http://dx.doi.org/10.1038/sj.onc.1206953] [PMID: 14576857]
[66]
Nies, A.T.; Keppler, D. The apical conjugate efflux pump ABCC2 (MRP2). Pflugers Arch., 2007, 453(5), 643-659.
[http://dx.doi.org/10.1007/s00424-006-0109-y] [PMID: 16847695]
[67]
Jedlitschky, G.; Hoffmann, U.; Kroemer, H.K. Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition. Expert Opin. Drug Metab. Toxicol., 2006, 2(3), 351-366.
[http://dx.doi.org/10.1517/17425255.2.3.351] [PMID: 16863439]
[68]
Keppler, D. Multidrug resistance proteins (MRPs, ABCCs): Importance for pathophysiology and drug therapy. Handb. Exp. Pharmacol., 2011, (201), 299-323.
[http://dx.doi.org/10.1007/978-3-642-14541-4_8] [PMID: 21103974]
[69]
Sandusky, G.E.; Mintze, K.S.; Pratt, S.E.; Dantzig, A.H. Expression of multidrug resistance-associated protein 2 (MRP2) in normal human tissues and carcinomas using tissue microarrays. Histopathology, 2002, 41(1), 65-74.
[http://dx.doi.org/10.1046/j.1365-2559.2002.01403.x] [PMID: 12121239]
[70]
Cui, Y.; König, J.; Buchholz, J.K.; Spring, H.; Leier, I.; Keppler, D. 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.
[PMID: 10220572]
[71]
Leier, I.; Jedlitschky, G.; Buchholz, U.; Keppler, D. Characterization of the ATP-dependent leukotriene C4 export carrier in mastocytoma cells. Eur. J. Biochem., 1994, 220(2), 599-606.
[http://dx.doi.org/10.1111/j.1432-1033.1994.tb18661.x] [PMID: 8125120]
[72]
Jedlitschky, G.; Leier, I.; Buchholz, U.; Hummel-Eisenbeiss, J.; Burchell, B.; Keppler, D. ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. Biochem. J., 1997, 327(Pt 1), 305-310.
[http://dx.doi.org/10.1042/bj3270305] [PMID: 9355767]
[73]
Kamisako, T.; Leier, I.; Cui, Y.; König, J.; Buchholz, U.; Hummel-Eisenbeiss, J.; Keppler, D. Transport of monoglucuronosyl and bisglucu-ronosyl bilirubin by recombinant human and rat multidrug resistance protein 2. Hepatology, 1999, 30(2), 485-490.
[http://dx.doi.org/10.1002/hep.510300220] [PMID: 10421658]
[74]
Ming, X.; Knight, B.M.; Thakker, D.R. Vectorial transport of fexofenadine across Caco-2 cells: Involvement of apical uptake and basolateral efflux transporters. Mol. Pharm., 2011, 8(5), 1677-1686.
[http://dx.doi.org/10.1021/mp200026v] [PMID: 21780830]
[75]
Tian, X.; Zamek-Gliszczynski, M.J.; Li, J.; Bridges, A.S.; Nezasa, K.; Patel, N.J.; Raub, T.J.; Brouwer, K.L.R. Multidrug resistance-associated protein 2 is primarily responsible for the biliary excretion of fexofenadine in mice. Drug Metab. Dispos., 2008, 36(1), 61-64.
[http://dx.doi.org/10.1124/dmd.107.017319] [PMID: 17913796]
[76]
Niemi, M.; Arnold, K.A.; Backman, J.T.; Pasanen, M.K.; Gödtel-Armbrust, U.; Wojnowski, L.; Zanger, U.M.; Neuvonen, P.J.; Eichelbaum, M.; Kivistö, K.T.; Lang, T. Association of genetic polymorphism in ABCC2 with hepatic multidrug resistance-associated protein 2 expres-sion and pravastatin pharmacokinetics. Pharmacogenet. Genomics, 2006, 16(11), 801-808.
[http://dx.doi.org/10.1097/01.fpc.0000230422.50962.91] [PMID: 17047488]
[77]
Leier, I.; Hummel-Eisenbeiss, J.; Cui, Y.; Keppler, D. ATP-dependent para-aminohippurate transport by apical multidrug resistance protein MRP2. Kidney Int., 2000, 57(4), 1636-1642.
[http://dx.doi.org/10.1046/j.1523-1755.2000.00007.x] [PMID: 10760098]
[78]
Smeets, P.H.E.; van Aubel, R.A.M.H.; Wouterse, A.C.; van den Heuvel, J.J.M.W.; Russel, F.G.M. Contribution of multidrug resistance pro-tein 2 (MRP2/ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter. J. Am. Soc. Nephrol., 2004, 15(11), 2828-2835.
[http://dx.doi.org/10.1097/01.ASN.0000143473.64430.AC] [PMID: 15504935]
[79]
Hooijberg, J.H.; Broxterman, H.J.; Kool, M.; Assaraf, Y.G.; Peters, G.J.; Noordhuis, P.; Scheper, R.J.; Borst, P.; Pinedo, H.M.; Jansen, G. Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Res., 1999, 59(11), 2532-2535.
[PMID: 10363967]
[80]
Huang, Y. Pharmacogenetics/genomics of membrane transporters in cancer chemotherapy. Cancer Metastasis Rev., 2007, 26(1), 183-201.
[http://dx.doi.org/10.1007/s10555-007-9050-6] [PMID: 17323126]
[81]
Dietrich, C.G.; de Waart, D.R.; Ottenhoff, R.; Schoots, I.G.; Elferink, R.P. Increased bioavailability of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in MRP2-deficient rats. Mol. Pharmacol., 2001, 59(5), 974-980.
[http://dx.doi.org/10.1124/mol.59.5.974] [PMID: 11306678]
[82]
Wacher, V.J.; Wu, C.Y.; Benet, L.Z. 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.
[http://dx.doi.org/10.1002/mc.2940130302] [PMID: 7619215]
[83]
Zhang, Y.; Benet, L.Z. The gut as a barrier to drug absorption: Combined role of cytochrome P450 3A and P-glycoprotein. Clin. Pharmacokinet., 2001, 40(3), 159-168.
[http://dx.doi.org/10.2165/00003088-200140030-00002] [PMID: 11327196]
[84]
Benet, L.Z.; Cummins, C.L. The drug efflux-metabolism alliance: Biochemical aspects. Adv. Drug Deliv. Rev., 2001, 50(Suppl. 1), S3-S11.
[http://dx.doi.org/10.1016/S0169-409X(01)00178-8] [PMID: 11576692]
[85]
Wacher, V.J.; Salphati, L.; Benet, L.Z. Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv. Drug Deliv. Rev., 2001, 46(1-3), 89-102.
[http://dx.doi.org/10.1016/S0169-409X(00)00126-5] [PMID: 11259835]
[86]
Gomez, D.Y.; Wacher, V.J.; Tomlanovich, S.J.; Hebert, M.F.; Benet, L.Z. The effects of ketoconazole on the intestinal metabolism and bioa-vailability of cyclosporine. Clin. Pharmacol. Ther., 1995, 58(1), 15-19.
[http://dx.doi.org/10.1016/0009-9236(95)90067-5] [PMID: 7628178]
[87]
Lown, K.S.; Mayo, R.R.; Leichtman, A.B.; Hsiao, H.L.; Turgeon, D.K.; Schmiedlin-Ren, P.; Brown, M.B.; Guo, W.; Rossi, S.J.; Benet, L.Z.; Watkins, P.B. Role of intestinal P-glycoprotein (MDR1) in interpatient variation in the oral bioavailability of cyclosporine. Clin. Pharmacol. Ther., 1997, 62(3), 248-260.
[http://dx.doi.org/10.1016/S0009-9236(97)90027-8] [PMID: 9333100]
[88]
Wandel, C.; Kim, R.B.; Kajiji, S.; Guengerich, P.; Wilkinson, G.R.; Wood, A.J. P-glycoprotein and cytochrome P-450 3A inhibition: Disso-ciation of inhibitory potencies. Cancer Res., 1999, 59(16), 3944-3948.
[PMID: 10463589]
[89]
Ghosal, A.; Satoh, H.; Thomas, P.E.; Bush, E.; Moore, D. Inhibition and kinetics of cytochrome P4503A activity in microsomes from rat, human, and cdna-expressed human cytochrome P450. Drug Metab. Dispos., 1996, 24(9), 940-947.
[PMID: 8886602]
[90]
Fan, Y.; Rodriguez-Proteau, R. Ketoconazole and the modulation of multidrug resistance-mediated transport in Caco-2 and MDCKII-MDR1 drug transport models. Xenobiotica, 2008, 38(2), 107-129.
[http://dx.doi.org/10.1080/00498250701744625] [PMID: 18197554]
[91]
Saad, A.H.; DePestel, D.D.; Carver, P.L. Factors influencing the magnitude and clinical significance of drug interactions between azole anti-fungals and select immunosuppressants. Pharmacotherapy, 2006, 26(12), 1730-1744.
[http://dx.doi.org/10.1592/phco.26.12.1730] [PMID: 17125435]
[92]
Dauchy, S.; Dutheil, F.; Weaver, R.J.; Chassoux, F.; Daumas-Duport, C.; Couraud, P.O.; Scherrmann, J.M.; De Waziers, I.; Declèves, X. ABC transporters, cytochromes P450 and their main transcription factors: Expression at the human blood-brain barrier. J. Neurochem., 2008, 107(6), 1518-1528.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05720.x] [PMID: 19094056]
[93]
Decleves, X.; Jacob, A.; Yousif, S.; Shawahna, R.; Potin, S.; Scherrmann, J.M. Interplay of drug metabolizing CYP450 enzymes and ABC transporters in the blood-brain barrier. Curr. Drug Metab., 2011, 12(8), 732-741.
[http://dx.doi.org/10.2174/138920011798357024] [PMID: 21623707]
[94]
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(2), 695-698.
[http://dx.doi.org/10.1073/pnas.86.2.695] [PMID: 2563168]
[95]
Nies, A.T.; Jedlitschky, G.; König, J.; Herold-Mende, C.; Steiner, H.H.; Schmitt, H.P.; Keppler, D. Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain. Neuroscience, 2004, 129(2), 349-360.
[http://dx.doi.org/10.1016/j.neuroscience.2004.07.051] [PMID: 15501592]
[96]
Warren, M.S.; Zerangue, N.; Woodford, K.; Roberts, L.M.; Tate, E.H.; Feng, B.; Li, C.; Feuerstein, T.J.; Gibbs, J.; Smith, B.; de Morais, S.M.; Dower, W.J.; Koller, K.J. Comparative gene expression profiles of ABC transporters in brain microvessel endothelial cells and brain in five species including human. Pharmacol. Res., 2009, 59(6), 404-413.
[http://dx.doi.org/10.1016/j.phrs.2009.02.007] [PMID: 19429473]
[97]
Taylor, E.M. The impact of efflux transporters in the brain on the development of drugs for CNS disorders. Clin. Pharmacokinet., 2002, 41(2), 81-92.
[http://dx.doi.org/10.2165/00003088-200241020-00001] [PMID: 11888329]
[98]
Wang, J.S.; DeVane, C.L.; Gibson, B.B.; Donovan, J.L.; Markowitz, J.S.; Zhu, H.J. Population pharmacokinetic analysis of drug-drug interac-tions among risperidone, bupropion, and sertraline in CF1 mice. Psychopharmacology (Berl.), 2006, 183(4), 490-499.
[http://dx.doi.org/10.1007/s00213-005-0209-y] [PMID: 16283256]
[99]
Choo, E.F.; Kurnik, D.; Muszkat, M.; Ohkubo, T.; Shay, S.D.; Higginbotham, J.N.; Glaeser, H.; Kim, R.B.; Wood, A.J.; Wilkinson, G.R. Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier. J. Pharmacol. Exp. Ther., 2006, 317(3), 1012-1018.
[http://dx.doi.org/10.1124/jpet.105.099648] [PMID: 16537797]
[100]
Girardin, F. Membrane transporter proteins: A challenge for CNS drug development. Dialogues Clin. Neurosci., 2006, 8(3), 311-321.
[http://dx.doi.org/10.31887/DCNS.2006.8.3/fgirardin] [PMID: 17117613]
[101]
FDA. In vitro drug interaction studies - cytochrome p450 enzyme and transporter mediated drug interactions 2020, 1
[102]
Varma, M.V.S.; Ashokraj, Y.; Dey, C.S.; Panchagnula, R. P-glycoprotein inhibitors and their screening: A perspective from bioavailability enhancement. Pharmacol. Res., 2003, 48(4), 347-359.
[http://dx.doi.org/10.1016/S1043-6618(03)00158-0] [PMID: 12902205]
[103]
Sarkadi, B.; Homolya, L.; Szakács, G.; Váradi, A. Human multidrug resistance ABCB and ABCG transporters: Participation in a chemoim-munity defense system. Physiol. Rev., 2006, 86(4), 1179-1236.
[http://dx.doi.org/10.1152/physrev.00037.2005] [PMID: 17015488]
[104]
Ishikawa, T.; Sakurai, A.; Kanamori, Y.; Nagakura, M.; Hirano, H.; Takarada, Y.; Yamada, K.; Fukushima, K.; Kitajima, M. High-speed screening of human ATP-binding cassette transporter function and genetic polymorphisms: New strategies in pharmacogenomics. Methods Enzymol., 2005, 400, 485-510.
[http://dx.doi.org/10.1016/S0076-6879(05)00027-3] [PMID: 16399366]
[105]
Shukla, S.; Robey, R.W.; Bates, S.E.; Ambudkar, S.V. The calcium channel blockers, 1,4-dihydropyridines, are substrates of the multidrug resistance-linked ABC drug transporter, ABCG2. Biochemistry, 2006, 45(29), 8940-8951.
[http://dx.doi.org/10.1021/bi060552f] [PMID: 16846237]
[106]
Song, J.; Melera, P.W. Further characterization of the sixth transmembrane domain of Pgp1 by site-directed mutagenesis. Cancer Chemother. Pharmacol., 2001, 48(5), 339-346.
[http://dx.doi.org/10.1007/s002800100354] [PMID: 11761450]
[107]
Deeley, R.G.; Westlake, C.; Cole, S.P. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol. Rev., 2006, 86(3), 849-899.
[http://dx.doi.org/10.1152/physrev.00035.2005] [PMID: 16816140]
[108]
Xia, C.Q.; Milton, M.N.; Gan, L.S. Evaluation of drug-transporter interactions using in vitro and in vivo models. Curr. Drug Metab., 2007, 8(4), 341-363.
[http://dx.doi.org/10.2174/138920007780655423] [PMID: 17504223]
[109]
Bakos, E.; Evers, R.; Sinkó, E.; Váradi, A.; Borst, P.; Sarkadi, B. Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol. Pharmacol., 2000, 57(4), 760-768.
[http://dx.doi.org/10.1124/mol.57.4.760] [PMID: 10727523]
[110]
Deeley, R.G.; Cole, S.P. Substrate recognition and transport by multidrug resistance protein 1 (ABCC1). FEBS Lett., 2006, 580(4), 1103-1111.
[http://dx.doi.org/10.1016/j.febslet.2005.12.036] [PMID: 16387301]
[111]
Suzuki, M.; Suzuki, H.; Sugimoto, Y.; Sugiyama, Y. ABCG2 transports sulfated conjugates of steroids and xenobiotics. J. Biol. Chem., 2003, 278(25), 22644-22649.
[http://dx.doi.org/10.1074/jbc.M212399200] [PMID: 12682043]
[112]
Volk, E.L.; Schneider, E. Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res., 2003, 63(17), 5538-5543.
[PMID: 14500392]
[113]
Cai, J.; Gros, P. Overexpression, purification, and functional characterization of ATP-binding cassette transporters in the yeast, Pichia pas-toris. Biochim. Biophys. Acta, 2003, 1610(1), 63-76.
[http://dx.doi.org/10.1016/S0005-2736(02)00718-6] [PMID: 12586381]
[114]
Evans, G.L.; Ni, B.; Hrycyna, C.A.; Chen, D.; Ambudkar, S.V.; Pastan, I.; Germann, U.A.; Gottesman, M.M. Heterologous expression sys-tems for P-glycoprotein: E. coli, yeast, and baculovirus. J. Bioenerg. Biomembr., 1995, 27(1), 43-52.
[http://dx.doi.org/10.1007/BF02110330] [PMID: 7629051]
[115]
Janvilisri, T.; Venter, H.; Shahi, S.; Reuter, G.; Balakrishnan, L.; van Veen, H.W. Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J. Biol. Chem., 2003, 278(23), 20645-20651.
[http://dx.doi.org/10.1074/jbc.M301358200] [PMID: 12668685]
[116]
Lee, S.H.; Altenberg, G.A. Expression of functional multidrug-resistance protein 1 in Saccharomyces cerevisiae: Effects of N- and C-terminal affinity tags. Biochem. Biophys. Res. Commun., 2003, 306(3), 644-649.
[http://dx.doi.org/10.1016/S0006-291X(03)01029-5] [PMID: 12810067]
[117]
Litman, T.; Druley, T.E.; Stein, W.D.; Bates, S.E. From MDR to MXR: New understanding of multidrug resistance systems, their properties and clinical significance. Cell. Mol. Life Sci., 2001, 58(7), 931-959.
[http://dx.doi.org/10.1007/PL00000912] [PMID: 11497241]
[118]
Ozvegy, C.; Litman, T.; Szakács, G.; Nagy, Z.; Bates, S.; Váradi, A.; Sarkadi, B. Functional characterization of the human multidrug trans-porter, ABCG2, expressed in insect cells. Biochem. Biophys. Res. Commun., 2001, 285(1), 111-117.
[http://dx.doi.org/10.1006/bbrc.2001.5130] [PMID: 11437380]
[119]
Holló, Z.; Homolya, L.; Davis, C.W.; Sarkadi, B. Calcein accumulation as a fluorometric functional assay of the multidrug transporter. Biochim. Biophys. Acta, 1994, 1191(2), 384-388.
[http://dx.doi.org/10.1016/0005-2736(94)90190-2] [PMID: 7909692]
[120]
Homolya, L.; Holló, Z.; Germann, U.A.; Pastan, I.; Gottesman, M.M.; Sarkadi, B. Fluorescent cellular indicators are extruded by the multi-drug resistance protein. J. Biol. Chem., 1993, 268(29), 21493-21496.
[http://dx.doi.org/10.1016/S0021-9258(20)80566-3] [PMID: 8104940]
[121]
Ozvegy-Laczka, C.; Cserepes, J.; Elkind, N.B.; Sarkadi, B. Tyrosine kinase inhibitor resistance in cancer: Role of ABC multidrug transport-ers. Drug Resist. Updat., 2005, 8(1-2), 15-26.
[http://dx.doi.org/10.1016/j.drup.2005.02.002] [PMID: 15939339]
[122]
Adachi, Y.; Suzuki, H.; Sugiyama, Y. Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm. Res., 2001, 18(12), 1660-1668.
[http://dx.doi.org/10.1023/A:1013358126640] [PMID: 11785684]
[123]
Imai, Y.; Asada, S.; Tsukahara, S.; Ishikawa, E.; Tsuruo, T.; Sugimoto, Y. Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol. Pharmacol., 2003, 64(3), 610-618.
[http://dx.doi.org/10.1124/mol.64.3.610] [PMID: 12920197]
[124]
Evers, R.; Zaman, G.J.; van Deemter, L.; Jansen, H.; Calafat, J.; Oomen, L.C.; Oude Elferink, R.P.; Borst, P.; Schinkel, A.H. Basolateral lo-calization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells. J. Clin. Invest., 1996, 97(5), 1211-1218.
[http://dx.doi.org/10.1172/JCI118535] [PMID: 8636432]
[125]
Schinkel, A.H.; Wagenaar, E.; van Deemter, L.; Mol, C.A.; 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(4), 1698-1705.
[http://dx.doi.org/10.1172/JCI118214] [PMID: 7560060]
[126]
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 the CNS disposition of amprenavir (141W94), an HIV protease inhibitor. Pharm. Res., 1999, 16(8), 1206-1212.
[http://dx.doi.org/10.1023/A:1018941328702] [PMID: 10468021]
[127]
Yokogawa, K.; Takahashi, M.; Tamai, I.; Konishi, H.; Nomura, M.; Moritani, S.; Miyamoto, K.; Tsuji, A. P-glycoprotein-dependent disposi-tion kinetics of tacrolimus: Studies in MDR1a knockout mice. Pharm. Res., 1999, 16(8), 1213-1218.
[http://dx.doi.org/10.1023/A:1018993312773] [PMID: 10468022]
[128]
Cooray, H.C.; Blackmore, C.G.; Maskell, L.; Barrand, M.A. Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport, 2002, 13(16), 2059-2063.
[http://dx.doi.org/10.1097/00001756-200211150-00014] [PMID: 12438926]
[129]
Zhou, S.; Schuetz, J.D.; Bunting, K.D.; Colapietro, A.M.; Sampath, J.; Morris, J.J.; Lagutina, I.; Grosveld, G.C.; Osawa, M.; Nakauchi, H.; Sorrentino, B.P. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat. Med., 2001, 7(9), 1028-1034.
[http://dx.doi.org/10.1038/nm0901-1028] [PMID: 11533706]
[130]
Jonker, J.W.; Buitelaar, M.; Wagenaar, E.; Van Der Valk, M.A.; Scheffer, G.L.; Scheper, R.J.; Plosch, T.; Kuipers, F.; Elferink, R.P.; Rosing, H.; Beijnen, J.H.; Schinkel, A.H. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc. Natl. Acad. Sci. USA, 2002, 99(24), 15649-15654.
[http://dx.doi.org/10.1073/pnas.202607599] [PMID: 12429862]
[131]
Zhou, S.; Morris, J.J.; Barnes, Y.; Lan, L.; Schuetz, J.D.; Sorrentino, B.P. Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc. Natl. Acad. Sci. USA, 2002, 99(19), 12339-12344.
[http://dx.doi.org/10.1073/pnas.192276999] [PMID: 12218177]
[132]
van Herwaarden, A.E.; Jonker, J.W.; Wagenaar, E.; Brinkhuis, R.F.; Schellens, J.H.; Beijnen, J.H.; Schinkel, A.H. The breast cancer re-sistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Res., 2003, 63(19), 6447-6452.
[PMID: 14559835]
[133]
Adachi, Y.; Suzuki, H.; Schinkel, A.H.; Sugiyama, Y. Role of breast cancer resistance protein (Bcrp1/Abcg2) in the extrusion of glucuronide and sulfate conjugates from enterocytes to intestinal lumen. Mol. Pharmacol., 2005, 67(3), 923-928.
[http://dx.doi.org/10.1124/mol.104.007393] [PMID: 15598971]
[134]
Merino, G.; Alvarez, A.I.; Pulido, M.M.; Molina, A.J.; Schinkel, A.H.; Prieto, J.G. Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone antibiotics and affects their oral availability, pharmacokinetics, and milk secretion. Drug Metab. Dispos., 2006, 34(4), 690-695.
[http://dx.doi.org/10.1124/dmd.105.008219] [PMID: 16434544]
[135]
Lorico, A.; Rappa, G.; Finch, R.A.; Yang, D.; Flavell, R.A.; Sartorelli, A.C. Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione. Cancer Res., 1997, 57(23), 5238-5242.
[PMID: 9393741]
[136]
Wijnholds, J.; Evers, R.; van Leusden, M.R.; Mol, C.A.A.M.; Zaman, G.J.R.; Mayer, U.; Beijnen, J.H.; van der Valk, M.; Krimpenfort, P.; Borst, P. Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein. Nat. Med., 1997, 3(11), 1275-1279.
[http://dx.doi.org/10.1038/nm1197-1275] [PMID: 9359705]
[137]
Dietrich, C.G.; Geier, A.; Oude Elferink, R.P. ABC of oral bioavailability: Transporters as gatekeepers in the gut. Gut, 2003, 52(12), 1788-1795.
[http://dx.doi.org/10.1136/gut.52.12.1788] [PMID: 14633964]
[138]
Zelcer, N.; van de Wetering, K.; Hillebrand, M.; Sarton, E.; Kuil, A.; Wielinga, P.R.; Tephly, T.; Dahan, A.; Beijnen, J.H.; Borst, P. Mice lack-ing multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Proc. Natl. Acad. Sci. USA, 2005, 102(20), 7274-7279.
[http://dx.doi.org/10.1073/pnas.0502530102] [PMID: 15886284]
[139]
van de Wetering, K.; Zelcer, N.; Kuil, A.; Feddema, W.; Hillebrand, M.; Vlaming, M.L.; Schinkel, A.H.; Beijnen, J.H.; Borst, P. Multidrug resistance proteins 2 and 3 provide alternative routes for hepatic excretion of morphine-glucuronides. Mol. Pharmacol., 2007, 72(2), 387-394.
[http://dx.doi.org/10.1124/mol.107.035592] [PMID: 17485564]