Interaction of Drug Transporters with Excipients

Role of Lipid Excipients in Modifying Oral and Parenteral Drug Delivery: Basic Principles and Biological Examples

Volumn , Issue , 2006, Pages 1-31

  Pang, K Sandy ^a   Liu, Lichuan ^b   Sun, Huadong ^b  

^a UNIVERSITY OF TORONTO   (Canada)

^b NONE

Author keywords

Drug transporter interaction with excipients; Drug transporter modulation by excipients and surfactants; Intestinal absorptive and efflux transporters

Indexed keywords

EID: 79955850537     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470097984.ch1     Document Type: Chapter

References (267)

1. Pang, K.S. Modeling of intestinal drug absorption: Roles of transporters and metabolic enzymes (for the Gillette Review Series). Drug Metab Dispos 2003;31:1507-1519.
2. Doherty, M., Pang, K.S. The role of the intestine in the absorption and metabolism of drugs. Drug Chem Toxicol 1997;20:329-344.
3. Tam, D., Tirona, R.G., Pang, K.S. Segmental intestinal transporters and metabolic enzymes on intestinal drug absorption. Drug Metab Dispos 2003;31:373-383.
4. Lin, J.H., Chiba, M., Baillie, T.A. Is the role of the small intestine in first-pass metabolism overemphasized? Pharmacol Rev 1999;51:125-158.
5. Trauner, M., Boyer, J.L. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 2003;83:633-671.
6. Eloranta, J.J., Meier, P.J., Kullak-Ublick, G.A. Coordinate transcriptional regulation of transport and metabolism. Methods Enzymol 2005;400:511-530.
7. Huang, Y., Anderle, P., Bussey, K.J., Barbacioru, C., Shankavaram, U., Dai, Z., et al. Membrane transporters and channels: role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Res 2004;64:4294-4301.
8. Tsuji, A., Tamai, I. Carrier-mediated intestinal transport of drugs. Pharm Res 1996;13:962-977.
9. Mizuno, N., Niwa, T., Yotsumoto, Y., Sugiyama, Y. Impact of drug transporter studies on drug discovery and development. Pharmacol Rev 2003;55:425-461.
10. Steffansen, B., Nielsen, C.U., Broden, B., Eriksson, A.H., Andersen, R., Frokjaer, S. Intestinal solute carriers: an overview of trends and strategies for improving oral drug absorption. Eur J Pharm Sci 2004;21:3-16.
11. Anderle, P., Huang, Y., Wolfgang, S. Intestinal membrane transport of drugs and nutrients: genomics of membrane transporters using expression microarrays. Eur J Pharm Sci 2004;21:17-24.
12. Gerk, P.M., Vore, M. Regulation of expression of the multidrug resistance-associated protein 2 (MRP2) and its role in drug disposition. J Pharmacol Exp Ther 2002;302:407-415.
13. Goodwin, B., Redinbo, M.R., Kliewer, S.A. Regulation of cyp3a gene transcription by the pregnane x receptor. Annu Rev Pharmacol Toxicol 2002;42:1-23.
14. Willson, T.M., Kliewer, S.A. PXR, CAR and drug metabolism. Nat Rev Drug Discov 2002;1:259-266.
15. Kliewer, S.A., Goodwin, B., Willson, T.M. The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocr Rev 2002;23:687-702.
16. Wang, H., LeCluyse, E.L. Role of orphan nuclear receptors in the regulation of drug-metabolising enzymes. Clin Pharmacokinet 2003;42:1331-1357.
17. Staudinger, J.L., Madan, A., Carol, K.M., Parkinson, A. Regulation of drug transporter gene expression by nuclear receptors. Drug Metab Dispos 2003;31:523-527.
18. Bock, K.W., Kohle, C. Coordinate regulation of drug metabolism by xenobiotic nuclear receptors: UGTs acting together with CYPs and glucuronide transporters. Drug Metab Rev 2004;36:595-615.
19. Haimeur, A., Conseil, G., Deeley, R.G., Cole, S.P. The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr Drug Metab 2004;5:21-53.
20. Catania, V.A., Sanchez Pozzi, E.J., Luquita, M.G., Ruiz, M.L., Villanueva, S.S., et al. Coregulation of expression of phase II metabolizing enzymes and multidrug resistance-associated protein 2. Ann Hepatol 2004;3:11-17.
21. Runge-Morris, M., Kocarek, T.A. Regulation of sulfotransferases by xenobiotic receptors. Curr Drug Metab 2005;6:299-307.
22. Eloranta, J.J., Kullak-Ublick, G.A. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch Biochem Biophys 2005;433:397-412.
23. Tirona, R.G., Kim, R.B. Nuclear receptors and drug disposition gene regulation. J Pharm Sci 2005;94:1169-1186.
24. Lammert, F., Wang, D.Q. New insights into the genetic regulation of intestinal cholesterol absorption. Gastroenterology 2005;129:718-734.
25. Plosch, T., Kosters, A., Groen, A.K., Kuipers, F. The ABC of hepatic and intestinal cholesterol transport. Handbook Exp Pharmacol 2005;170:465-482.
26. Terada, T., Shimada, Y., Pan, X., Kishimoto, K., Sakurai, T., Doi, R., et al. Expression profiles of various transporters for oligopeptides, amino acids and organic ions along the human digestive tract. Biochem Pharmacol 2005;70:1756-1763.
27. Anderson, C.M., Grenade, D.S., Boll, M., Foltz, M., Wake, K.A., Kennedy, D.J., et al. H+/amino acid transporter 1 (PAT1) is the imino acid carrier: An intestinal nutrient/drug transporter in human and rat. Gastroenterology 2004;127:1410-1422.
28. Bell, G.I., Kayano, T., Buse, J.B., Burant, C.F., Takeda, J., Lin, D., et al. Molecular biology of mammalian glucose transporters. Diabetes Care 1990;13:198-208.
29. Stahl, A. Acurrent review of fatty acid transport proteins (SLC27). Plügers Arch 2005;447:772-777.
30. Hirch, D., Stahl, A., Lodish, H.F. A family of fatty acid transporters conserved from mycobacteria to man. Proc Natl Acad Sci USA 1998;95:8625-8629.
31. Abumed, N.A., el-Maghrabi, M.R., Amri, E.Z., Lozep, E., Grimaldi, P.A. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. J Biol Chem 1993;268:17665-17668.
32. Brinckmann, J.F.F., Abumrad, N.A., Ibrahimi, A., Vusse, G.V.D., Glatz, J.F. New insights in long chain fatty acid uptake by heart muscle: crucial role for fatty acid translocase/CD36. Biochem J 2002;367:561-570.
33. Besnard, P., Niot, I., Bernard, A., Carlier, H. Cellular and molecular aspects of fat metabolism in the small intestine. Proc Nutr Soc 1996;55:19-37.
34. Takanaga, H., Mackenzie, B., Hediger, M.A. Sodium-dependent ascorbic acid transporter family SLC23. Pflügers Arch 2004;447:677-682.
35. Dudeja, P.K., Kode, A., Alnounou, M., Tyagi, S., Torania, S., Subramanian, V.S., Said, H.M. Mechanism of folate transport across the human colonic basolateral membrane. Am J Physiol Gastrointest Liver Physiol 2001;281:G54-G60.
36. Said, H.M., Ortiz, A., Kumar, C.K., Chatterjee, N., Dudeja, P.K., Rubin, S. Transport of thiamine in human intestine: mechanism and regulation in intestinal epithelial cell model Caco-2. Am J Physiol 1999;277(4 Pt 1):C645-C651.
37. Dudeja, P.K., Tyagi, S., Kavilaveettil, R.J., Gill, R., Said, H.M. Mechanism of thiamine uptake by human jejunal brush-border membrane vesicles. Am J Physiol Cell Physiol 2001;281:C786-C792.
38. Dudeja, P.K., Tyagi, S., Gill, R., Said, H.M. Evidence for a carrier-mediated mechanism for thiamine transport to human jejunal basolateral membrane vesicles. Dig Dis Sci 2003;48:109-115.
39. Wong, M.H., Rao, P.N., Pettenati, M.J., Dawson, P.A. Localization of the ileal sodium-bile acid cotransporter gene (SCL10A2) to human chromosome 13q33. Genomics 1996;33:536-540.
40. Shneider, B.L., Setchell, K.D., Crossman, M.W. Fetal and neonatal expression of the apical sodiumdependent bile acid transporter in the rat ileum and kidney. Pediatr Res 1997;42:189-194.
41. Craddock, A.L., Love, M.W., Daniel, R.W., Kirby, L.C., Walters, H.C., Wong, M.H., Dawson, P.A. Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol 1998;274(1 Pt 1):G157-G169.
42. Small, D.M., Dowling, R.H., Redinger, R.N. The enterohepatic circulation of bile salts. Arch Intern Med 1972;130:552-573.
43. Love, M.W., Craddock, A.L., Angelin, B., Brunzell, J.D., Duane, W.C., Dawson, P.A. Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia. Arterioscler Thromb Vasc Biol 2001;21:2039-2045.
44. Oelkers, P., Kirby, L.C., Heubi, J.E., Dawson, P.A. Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). J Clin Invest 1997;99:1880-1887.
45. Montagnani, M., Love, M.W., Rossel, P., Dawson, P.A., Qvist, P. Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption. Scand J Gastroenterol 2001;236:1077-1080.
46. Lewis, M.C., Brieaddy, L.E., Root, C. Effects of 2164U90 on ileal bile acid absorption and serum cholesterol in rats and mice. J Lipid Res 1995;36:1098-1105.
47. Xu, G., Shneider, B.L., Shefer, S., Nguyen, L.B., Batta, A.K., Tint, G.S., et al. Ileal bile acid transport regulates bile acid pool, synthesis, and plasma cholesterol levels differently in cholesterol-fed rats and rabbits. J Lipid Res 2000;41:298-304.
48. Dawson, P.A., Hubbert, M., Haywood, J., Craddock, A.L., Zerangue, N., Christian, W.V., Ballatori, N. The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter. J Biol Chem 2005;280:6960-6968.
49. Shoji, T., Suzuki, H., Kusuhara, H., Watanabe, Y., Sakamoto, S., Sugiyama, Y. ATP-dependent transport of organic anions into isolated basolateral membrane vesicles from rat intestine. Am J Physiol Gastrointest Liver Physiol 2004;287:G749-G756.
50. Daniel, H. Molecular and integrative physiology of intestinal peptide transport. Annu Rev Physiol 2004;66:361-384.
51. Fei, Y.J., Kanai, Y., Nussberger, Y., Ganapathy, V., Leibach, F.H., Romero, M.F., et al. Expression cloning of a mammalian proton coupled oligopeptide transporter. Nature 1994;368:563-566.
52. Boll, M., Markovich, D., Weber, W.M., Korte, H., Daniel, H., Murer, H. Expression cloning of a cDNAfrom rabbit small intestine related to proton-coupled transport of peptides, beta-lactam antibiotics and ACE-inhibitors. Pflügers Arch 1994;429:146-149.
53. Horie, R., Tomita, Y., Katsura, T., Yasuhara, M., Inui, K., Takano, M. (Transport of bestatin in rat renal brush-border membrane vesicles. Biochem Pharmacol 1993;45:1763-1768.
54. Ganapathy, M.E., Brandsch, M., Prasad, P.D., Ganapathy, V., Leibach, F.H. Differential recognition of beta-lactam antibiotics by intestinal and renal peptide transporters PEPT1 and PEPT2. J Biol Chem 1995;270:25672-25677.
55. Ganapathy, M.E., Prasad, P.D., Mackenzie, B., Ganapathy, V., Leibach, F.H. Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim Biophys Acta 1997;1324:251-262.
56. Han, H.K., Rhie, J.K., Oh, D.M., Saito, G., Hsu, C.P., Stewart, B.H., Amidon, G.L. CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs. J Pharm Sci 1999;88:347-350.
57. Buyse, M., Berlioz, F., Guilmeau, S., Tsocas, A., Voisin, T., Peranzi, G., et al. PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine. J Clin Invest 2001;108:1483-1494.
58. Beauchamp, L.M., Orr, G.F., Miranada, P., Burnette, T., Krenistsky, T.A. Amino ester prodrugs of aciclovir. Antiviral Chem Chemother 1992;3:157-164.
59. Ganapthy, M.E., Huang, W., Wng, H., Ganapthay, V. Valaciclovir: a substrate for the intestinal and renal peptide transporter PepT1 and PepT2. Biochem Biophys Res Commun 1998;246:470-475.
60. Steingrimsdottir, H., Gruber, A., Palm, C., Grimfors, G., Kahn, M., Eksborg, S. Bioavailability of aciclovir after oral administration of aciclovir and its prodrug valaciclovir to patients with leucopenia after chemotherapy. Antimicrob Agents Chemother 2000;44:207-209.
61. Han, H., de Vrueh, R.L., Rhie, J.K., Covitz, K.M., Smith, P.L., Lee, C.P., et al. 5′-Amino acid esters of antiviral nucleosides, acyclovir and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharm Res 1998;15:1154-1159.
62. Tsuda, M., Terada, T., Irie, M., Katsura, T., Niida, A., Tomita, K., et al. Transport Characteristics of a novel PEPT1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther 2006;Apr 5 [Epub ahead of print].
63. Brandsch, M., Knutter, I., Leibach, F.H. The intestinal H+/peptide symporter PEPT1: structureaffinity relationships. Eur J Pharm Sci 2004;21:53-60.
64. Anderle, P., Nielsen, C.U., Pinsonneault, J., Krog, P.L., Brodin, B., Sadee, W. Genetic variants of the human dipeptide transporter PEPT1. J Pharmacol Exp Ther 2006;316:636-646.
65. Sundaram, U., Wisel, S., Coon, S. Mechanism of inhibition of proton: dipeptide co-transport during chronic enteritis in the mammalian small intestine. Biochim Biophys Acta 2005;1714:134-140.
66. Tamai, I., Nezu, J., Uchino, H., Sai, Y., Oku, A., Shimane, M., Tsuji, A. Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun 2000;273:251-260.
67. Hagenbuch, B., Meier, P.J. The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta 2003;1609:1-18.
68. Nozawa, T., Imai, K., Nezu, J., Tsuji, A., Tamai, I. Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther 2004; 308:438-445.
69. Kobayashi, D., Nozawa, T., Imai, K., Nezu, J., Tsuji, A., Tamai, I. Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J Pharmacol Exp Ther 2003;306:703-708.
70. Satoh, H., Yamashita, F., Tsujimoto, M., Murakami, H., Koyabu, N., Ohtani, H., Sawada, Y. Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 2005;33:518-523.
71. Kopplow, K., Letschert, K., Konig, J., Walter, B., Keppler, D. Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. Mol Pharmacol 2005;68:1031-1038.
72. Kullak Ublick, G.A., Beuers, U., Fahney, C., Hagenbuch, B., Meier, P.J., Paumgartner, G. Identification and functional characterization of the promoter region of the human organic anion transporting polypeptide gene. Hepatology 1997;26:991-997.
73. Cvetkovic, M., Leake, B., Fromm, M.F., Wilkinson, G.R., Kim, R.B. OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos 1999;27:866-871.
74. Su, Y., Zhang, X., Sinko, P.J. Human organic anion-transporting polypeptide OATP-A (SLC21A3) acts in concert with P-glycoprotein and multidrug resistance protein 2 in the vectorial transport of Saquinavir in Hep G2 cells. Mol Pharm 2004;1:49-56.
75. Dresser, G.K., Kim, R.B., Bailey, D.G. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Clin Pharmacol Ther 2005;77:170-177.
76. Fuchikami, H., Satoh, H., Tsujimoto, M., Ohdo, S., Ohtani, H., Sawada, Y. Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 2006;34:577-582.
77. Lu, R., Kanai, N., Bao, Y., Schuster, V.L. Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA (hPGT). J Clin Invest 1996;98:1142-1149.
78. Garcia, C.K., Goldstein, J.L., Pathak, R.K., Anderson, R.G., Brown, M.S. Other monocarboxylates: implications for the Cori cycle. Cell 1994;76:865-873.
79. Ritzhaupt, A., Wood, I.S., Ellis, A., Hosie, K.B., Shirazi-Beechey, S.P. Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L-lactate as well as butyrate. J Physiol 1998;513(Pt 3):719-732.
80. Tamai, I., Sai, Y., Ono, A., Kido, Y., Yabuuchi, H., Takanaga, H., et al. Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol 1999;51:1113-1121.
81. Stein, J., Zores, M., Schroder, O. Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pHdependent and carrier mediated transport mechanism. Eur J Nutr 2000;39:121-125.
82. Hadjiagapiou, C., Schmidt, L., Dudeja, P.K., Layden, T.J., Ramaswamy, K. Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1. Am J Physiol Gastrointest Liver Physiol 2000;279:G775-G780.
83. Halestrap, A.P., Price, N.T. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 1999;343(Pt 2):281-299.
84. Buyse, M., Sitaraman, S.V., Liu, X., Bado, A., Merlin, D. Luminal leptin enhances CD147/MCT-1-mediated uptake of butyrate in the human intestinal cell line Caco2-BBE. J Biol Chem 2002;277:28182-28190.
85. Gill, R.K., Saksena, S., Alrefai, W.A., Sarwar, Z., Goldstein, J.L., Carroll, R.E., et al. Expression and membrane localization of MCT isoforms along the length of the human intestine. Am J Physiol Cell Physiol 2005;289:C846-C852.
86. Murer, H., Markovich, D., Biber, J. Renal and small intestinal sodium-dependent symporters of phosphate and sulphate. J Exp Biol 1994;196:167-181.
87. Xu, H., Bai, L., Collins, J.F., Ghishan, F.K. Molecular cloning, functional characterization, tissue distribution, and chromosomal localization of a human, small intestinal sodium-phosphate (Na+-Pi) transporter (SLC34A2). Genomics 1999;62:281-284.
88. Feild, J.A., Zhang, L., Brun, K.A., Brooks, D.P., Edwards, R.M. Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine. Biochem Biophys Res Commun 1999;258:578-582.
89. Markovich, D., Regeer, R.R., Kunzelmann, K., Dawson, P.A. Functional characterization and genomic organization of the human Na(+)-sulfate cotransporter hNaS2 gene (SLC13A4). Biochem Biophys Res Commun 2005;326:729-734.
90. Swaan, P.W., Tukker, J.J. 1995 Carrier-mediated transport mechanism of foscarnet (trisodium phosphonoformate hexahydrate) in rat intestinal tissue. J Pharmacol Exp Ther 1995;272:242-247.
91. Loghman-Adham, M., Motock, G.T., Levi, M. Enhanced bioavailability of phosphonoformic acid by dietary phosphorus restriction. Biochem Pharmacol 1994;48:1455-1458.
92. Griffiths, M., Beaumont, N., Yao, S.Y., Sundaram, M., Boumah, C.E., Davies, A., et al. Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs. Nat Med 1997;3:89-93.
93. Ritzel, M.W., Yao, S.Y., Huang, M.Y., Elliott, J.F., Cass, C.E., Young, J.D. Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am J Physiol 1997;272(2 Pt 1):C707-C714.
94. Ritzel, M.W., Yao, S.Y., Ng, A.M., Mackey, J.R., Cass, C.E., Young, J.D. Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine. Mol Membr Biol 1998; 15:203-211.
95. Ritzel, M.W., Ng, A.M., Yao, S.Y., Graham, K., Loewen, S.K., Smith, K.M., et al. Recent molecular advances in studies of the concentrative Na+-dependent nucleoside transporter (CNT) family: identification and characterization of novel human and mouse proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). Mol Membr Biol 2001;18:65-72.
96. Carpenter, P., Chen, X.Z., Karpinski, E., Hyde, R.J., Baldwin, S.A., Cass, C.E., Young, J.D. Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J Biol Chem 2001;276:2914-2927.
97. Patil, S.D., Unadkat, J.D. Sodium-dependent nucleoside transport in the human intestinal brushborder membrane. Am J Physiol 1997;272:1314-1320.
98. Wang, J., Su, S.F., Dresser, M.J., Schaner, M.E., Washington, C.B., Giacomini, K.M. Na(+)-dependent purine nucleoside transporter from human kidney: cloning and functional characterization. Am J Physiol 1997;273(6 Pt 2):F1058-F1065.
99. Mata, J.F., Garcia-Manteiga, J.M., Lostao, M.P., Fernandez-Veledo, S., Guillen-Gomez, E., Larrayoz, I.M., et al. Role of the human concentrative nucleoside transporter (hCNT1) in the cytotoxic action of 5′-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug. Mol Pharmacol 2001;59:1542-1548.
100. Shin, H.C., Landowski, C.P., Sun, D., Vig, B.S., Kim, I., Mittal, S., et al. Functional expression and characterization of a sodium-dependent nucleoside transporter hCNT2 cloned from human duodenum. Biochem Biophys Res Commun 2003;307:696-703.
101. Graham, K.A., Leithoff, J., Coe, I.R., Mowles, D., Mackey, J.R., Young, J.D., Cass, C.E. Differential transport of cytosine-containing nucleosides by recombinant human concentrative nucleoside transporter protein hCNT1. Nucleosides Nucleotides Nucleic Acids 2000;19:415-434.
102. Chandrasena, G., Giltay, R., Patil, S.D., Bakken, A., Unadkat, J.D. Functional expression of human intestinal Na+-dependent and Na+-independent nucleoside transporters in Xenopus laevis oocytes. Biochem Pharmacol 1997;53:1909-1918.
103. Yao, S.Y., Ng, A.M., Sundaram, M., Cass, C.E., Baldwin, S.A., Young, J.D. Transport of antiviral 3′-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol Membr Biol 2001;18:161-167.
104. Ngo, L.Y., Patil, S.D., Unadkat, J.D. Ontogenic and longitudinal activity of Na(+)-nucleoside transporters in the human intestine. Am J Physiol Gastrointest Liver Physiol 2001;280:G475-G481.
105. Gründemann, D., Gorboulev, V., Gambaryan, S., Veyhl, M., Koepsell, H. Drug excretion mediated by a new prototype of polyspecific transporter. Nature 1994;372:549-552.
106. Koepsell, H. Organic cation transporters in intestine, kidney, liver, and brain. Annu Rev Physiol 1998;60:243-266.
107. Muller, J., Lips, K.S., Metzner, L., Neubert, R.H., Koepsell, H., Brandsch, M. Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Biochem Pharmacol 2005;70:1851-1860.
108. Martel, F., Keating, E., Calhau, C., Azevedo, I. Uptake of (3)H-1-methyl-4-phenylpyridinium ((3)HMPP(+)) by human intestinal Caco-2 cells is regulated by phosphorylation/dephosphorylation mechanisms. Biochem Pharmacol 2002;63:1565-1515.
109. Takeda, M., Khamdang, S., Narikawa, S., Kimura, H., Kobayashi, Y., Yamamoto, T., et al. Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther 2002;300:918-924.
110. Tamai, I., Ohashi, R., Nezu, J., Yabuuchi, H., Oku, A., Shimane, M., Sai, Y., Tsuji, A. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 1998;273:20378-20382.
111. Elimrani, I., Lahjouji, K., Seidman, E., Roy, M.J., Mitchell, G.A., Qureshi, I. Expression and localization of organic cation/carnitine transporter OCTN2 in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol 2003;284:G863-G871.
112. Ohashi, R., Tamai, I., Nezu Ji, J., Nikaido, H., Hashimoto, N., Oku, A., et al. Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol 2001;59:358-366.
113. Ganapathy, M.E., Huang, W., Rajan, D.P., Carter, A.L., Sugawara, M., Iseki, K., et al. Beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem 2000;275:1699-1707.
114. Duran, J.M., Peral, M.J., Calonge, M.L., Ilundain, A.A. OCTN3: A Na+-independent L-carnitine transporter in enterocytes basolateral membrane. J Cell Physiol 2005;202:929-935.
115. Altmann, S.W., Davis, H.R., Jr, Zhu, L.J., Yao, X., Hoos, L.M., Tetzloff, G., et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 2004;303:1201-1204.
116. Davis, H.R., Jr, Zhu, L.J., Hoos, L.M., Tetzloff, G., Maguire, M., Liu, J., et al. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J Biol Chem 2004;279:33586-33592.
117. Lally, S., Tan, C.Y., Owens, D., Tomkin, G.H. Messenger RNA levels of genes involved in dysregulation of postprandial lipoproteins in type 2 diabetes: the role of Niemann-Pick C1-like 1, ATPbinding cassette, transporters G5 and G8, and of microsomal triglyceride transfer protein. Diabetologia 2006;49:1008-1016.
118. Higgins, C.F. ABC transporters: from microorganism to man. Annu Rev Cell Biol 1992;8:67-113.
119. Dietrich, C.G., Geier, A., Oude Elferink, R.P. ABC of oral bioavailability: transporters as gatekeepers in the gut. Gut 2003;52:1788-1795.
120. Dean, M., Hamon, Y., Chimini, G. The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 2001;42:1007-1017.
121. Schinkel, A.H., Jonker, J.W. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 2003;55:3-29.
122. Ambudkar, S.V., Dey, S., Hrycyna, C.A., Ramachandra, M., Pastan, I., Gottesman, M.M. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol 1999;39:361-398.
123. Hoffmann, U., Kroemer, H.K. The ABC transporters MDR1 and MRP2: multiple functions in disposition of xenobiotics and drug resistance. Drug Metab Rev 2004;36:669-701.
124. Ambudkar, S.V., Kim, I.W., Sauna, Z.E. The power of the pump: mechanisms of action of Pglycoprotein (ABCB1). Eur J Pharm Sci 2006;27:392-400.
125. Dey, S., Ramachandra, M., Pastan, I., Gottesman, M.M., Ambudkar, S.V. Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proc Natl Acad Sci USA 1997;94:10594-10599.
126. Gottesman, M.M., Ling, V. The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research. FEBS Lett 2006;580:998-1009.
127. Takara, K., Tanigawara, Y., Komada, F., Nishiguchi, K., Sakaeda, T., Okumura, K. Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull 1999;22:1355-1359.
128. Troutman, M.D., Thakker, D.R. Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res 2003;20:1210-1224.
129. 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.
130. Lecureur, V., Sun, D., Hargrove, P., Schuetz, E.G., Kim, R.B., Lan, L.B., Schuetz, J.D. Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol 2000;57:24-35.
131. Collett, A., Tanianis-Hughes, J., Hallifax, D., Warhurst, G. Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res 2004;21:819-826.
132. Taipalensuu, J., Tavelin, S., Lazorova, L., Svensson, A.C., Artursson, P. Exploring the quantitative relationship between the level of MDR1 transcript, protein and function using digoxin as a marker of MDR1-dependent drug efflux activity. Eur J Pharm Sci 2004;21:69-75.
133. Ueda, K., Cardarelli, C., Gottesman, M.M., Pastan, I. Expression of a full-length cDNA for the human 'MDR1' gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci USA 1987;84:3004-3008.
134. Kim, R.B., Fromm, M.F., Wandel, C., Leake, B., Wood, A.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.
135. Alsenz, J., Steffen, H., Alex, R. Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in Caco-2 cell monolayers. Pharm Res 1998;15:423-428.
136. 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;16:1206-1212.
137. Saeki, T., Ueda, K., Tanigawara, Y. Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem 1993;268:6077-6080.
138. Goto, M., Masuda, S., Saito, H., Inui, K. Decreased expression of P-glycoprotein during differentiation in the human intestinal cell line Caco-2. Biochem Pharmacol 2003;66:163-70.
139. Ito, T., Yano, I., Tanaka, K., Inui, K.I. Transport of quinolone antibacterial drugs by human Pglycoprotein expressed in a kidney epithelial cell line, LLC-PK1. J Pharmacol Exp Ther 1997;282: 955-960.
140. Naruhashi, K., Tamai, I., Inoue, N., Muraoka, H., Sai, Y., Suzuki, N., Tsuji, A. Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein. J Pharm Pharmacol 2001;53:699-709.
141. Sun, H., Huang, Y., Frassetto, L., Benet, L.Z. Effects of uremic toxins on hepatic uptake and metabolism of erythromycin. Drug Metab Dispos 2004;32:1239-1246.
142. Ueda, K., Okamura, N., Hirai, M., Tanigawara, Y., Saeki, T., Kioka, N., et al. Human Pglycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem 1992;267:24248-24252.
143. Kim, W.Y., Benet, L.Z. P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm Res 2004;21:1284-1293.
144. Oka, A., Oda, M., Saitoh, H., Nakayama, A., Takada, M., Aungst, B.J. Secretory transport of methylprednisolone possibly mediated by P-glycoprotein in Caco-2 cells. Biol Pharm Bull 2002;25:393-396.
145. Karlsson, J., Kuo, S.M., Ziemniak, J., Artursson, P. Transport of celiprolol across human intestinal epithelial (Caco-2) cells: mediation of secretion by multiple transporters including P-glycoprotein. Br J Pharmacol 1993;110:1009-1016.
146. Soldner, A., Benet, L.Z., Mutschler, E., Christians, U. Active transport of the angiotensin-II antagonist losartan and its main metabolite EXP 3174; across MDCK-MDR1 and caco-2 cell monolayers. Br J Pharmacol 2000;129:1235-1243.
147. Saeki, T., Ueda, K., Tanigawara, Y., Hori, R., Komano, T. P-glycoprotein-mediated transcellular transport of MDR-reversing agents. FEBS Lett 1993;324:99-102.
148. Lee, K., Ng, C., Brouwer, K.L.R., Thakker, D.R. Secretory transport of ranitidine and famotidine across Caco-2 cell monolayers. J Pharmacol Exp Ther 2002;303:574-580.
149. Lentz, K.A., Polli, J.W., Wring, S.A., Humphreys, J.E., Polli, J.E. Influence of passive permeability on apparent p-glycoprotein kinetics. Pharm Res 2000;17:1456-1460.
150. Soares-Da-Silva, P., Serrao, M.P. Outward transfer of dopamine precursor L-3,4-dihydroxyphenylalanine (L-dopa) by native and human P-glycoprotein in LLC-PK(1) and LLC-GA5 col300 renal cells. J Pharmacol Exp Ther 2000;293:697-704.
151. Borgnia, M.J., Eytan, G.D., Assaraf, Y.G. Competition of hydrophobic peptides, cytotoxic drugs, and chemosensitizers on a common P-glycoprotein pharmacophore as revealed by its ATPase activity. J Biol Chem 1996;2716:3163-3171.
152. Lang, V.B., Langguth, P., Ottiger, C., Wunderli-Allenspach, H., Rognan, D., Rothen-Rutishauser, B., et al. Structure-permeation relations of met-enkephalin peptide analogues on absorption and secretion mechanisms in Caco-2 monolayers. J Pharm Sci 1997;86:846-853.
153. Faassen, F., Vogel, G., Spanings, H., Vromans, H. Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm 2003;263:113-122.
154. Schinkel, A.H., Wagenaar, E., van Deemter, L., Mol, C.A., Borst, P. Absence of the mdr1a PGlycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin, A. J Clin Invest 1995;96:1698-1705.
155. Kim, R.B., Wandel, C., Leake, B., Cvetkovic, M., Fromm, M.F., Dempsey, P.J., et al. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res 1999;16:408-414.
156. Smit, J.W., Weert, B., Schinkel, A.H., Meijer, D.K. Heterologous expression of various Pglycoproteins in polarized epithelial cells induces directional transport of small (type 1) and bulky (type 2) cationic drugs. J Pharmacol Exp Ther 1998;286:321-327.
157. van der Sandt, I.C., Smolders, R., Nabulsi, L., Zuideveld, K.P., de Boer, A.G., Breimer, D.D. Active efflux of the 5-HT(1A) receptor agonist flesinoxan via P-glycoprotein at the blood-brain barrier. Eur J Pharm Sci 2001;14:81-86.
158. Crowe, A. The influence of P-glycoprotein on morphine transport in Caco-2 cells. Comparison with paclitaxel. Eur J Pharmacol 2002;440:7-16.
159. Kharasch, E.D., Hoffer, C., Whittington, D., Sheffels, P. Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine. Clin Pharmacol Ther 2003;74:543-554.
160. Eichelbaum, M., Fromm, M.F., Schwab, M. Clinical aspects of the MDR1 (ABCB1) gene polymorphism. Ther Drug Monit 2004;26:180-185.
161. Hidalgo, I.J., Raub, T.J., Borchardt, R.T. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 1989;96:736-749.
162. Hunter, J., Jepson, M.A., Tsuruo, T., Simmons, N.L., Hirst, B.H. Functional expression of Pglycoprotein in apical membranes of human intestinal Caco-2 cells. Kinetics of vinblastine secretion and interaction with modulators. J Biol Chem 1993;268:14991-14997.
163. Collett, A., Tanianis-Hughes, J., Carlson, G.L., Harwood, M.D., Warhurst, G. Comparison of Pglycoprotein-mediated drug-digoxin interactions in Caco-2 with human and rodent intestine: relevance to in vivo prediction. Eur J Pharm Sci 2005;26:386-393.
164. Maki, N., Hafkemeyer, P., Dey, S. Allosteric modulation of human P-glycoprotein. Inhibition of transport by preventing substrate translocation and dissociation. J Biol Chem 2003;278: 18132-18139.
165. Fojo, T., Bates, S. Strategies for reversing drug resistance. Oncogene 2003;22:7512-7523.
166. Mamot, C., Drummond, D.C., Hong, K., Kirpotin, D.B., Park, J.W. Liposome-based approaches to overcome anticancer drug resistance. Drug Resist Update 2003;6:271-279.
167. Limtrakul, P., Khantamat, O., Pintha, K. Inhibition of P-glycoprotein function and expression by kaempferol and quercetin. J Chemother 2005;17:86-95.
168. Zhang, S., Morris, M.E. Effects of flavonoids biochanin, A., morin, phloretin, and silymarin on Pglycoprotein-mediated transport. J Pharmacol Exp Ther 2003;304:1258-1267.
169. Zhou, S., Lim, L.Y., Chowbay, B. Herbal modulation of P-glycoprotein. Drug Metab Rev 2004;36:57-104.
170. Morris, M.E., Zhang, S. Flavonoid-drug interactions: Effects of flavonoids on ABC transporters. Life Sci 2006;78:2116-2130.
171. Lown, K.S., Bailey, D.G., Fontana, R.J., Janardan, S.K., Adair, C.H., Fortlage, L.A., et al. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal protein expression. J Clin Invest 1997;99:2545-2553.
172. He, K., Iyer, K.R., Hayes, R.N., Sinz, M.W., Woolf, T.F., Hollenberg, P.F. Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol 1998;11:252-259.
173. Eagling, V.A., Profit, L., Back, D.J. Inhibition of the CYP3A4-mediated metabolism and Pglycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol 1999;48:543-552.
174. Becquemont, L., Verstuyft, C., Kerb, R., Brinkman, U., Lebot, M., Jaillon, P., Funch-Brentano, C. Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin Pharmacol Ther 2000;70:311-316.
175. Greenblatt, D.J., von Moltke, L.L., Harmatz, H.S., Chen, G., Weemhoff, J.L., Jen, C., et al. Time course of recovery of cytochrome P450 3A function after single doses of grapefruit juice. Clin Pharmacol Ther 2003;74:121-129.
176. Borst, P., Evers, R., Kool, M., Wijnholds, J. A family of drug transporters: the multidrug resistanceassociated proteins. J Natl Cancer Inst 2000;92:1295-1302.
177. Keppler, D., Cui, Y., Konig, J., Leier, I., Nies, A. Export pumps for anionic conjugates encoded by MRP genes. Adv Enzyme Regul 1999;39:237-246.
178. Taipalensuu, J., Tornblom, H., Lindberg, G., Einarsson, C., Sjoqvist, F., Melhus, H., et al. Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers. J Pharmacol Exp Ther 2001;299:164-170.
179. Büchler, M., Konig, J., Brom, M., Kartenbeck, J., Spring, H., Horie, T., Keppler, D. cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J Biol Chem 1996;271: 15091-15098.
180. Jedlitschky, G., Leier, I., Buchholz, U., Hummel-Eisenbeiss, J., Burchell, B., Keppler, D. ATPdependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. Biochem J 1997;327:305-310.
181. Kartenbeck, J., Leuschner, U., Mayer, R., Keppler, D. Absence of the canalicular isoform of the MRP gene-encoded conjugate export pump from the hepatocytes in Dubin-Johnson syndrome. Hepatology 1996;23:1061-1066.
182. Paulusma, C.C., Kool, M., Bosma, P.J., Scheffer, G.L., ter Borg, F., Scheper, R.J., et al. A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome. Hepatology 1997;25:1539-1542.
183. Huisman, M.T., Smit, J.W., Crommentuyn, K.M., Zelcer, N., Wiltshire, H.R., Beijnen, J.H., Schinkel, A.H. Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS 2002;16:2295-2301.
184. Huisman, M.T., Chhatta, A.A., van Tellingen, O., Beijnen, J.H., Schinkel, A.H. MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. Int J Cancer 2005;116:824-829.
185. Cui, Y., Konig, 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;55:929-937.
186. Evers, R., de Haas, M., Sparidans, R., Beijnen, J., Wielinga, P.R., Lankelma, J., Borst, P. Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer 2000;83:375-383.
187. Sasaki, M., Suzuki, H., Ito, K., Abe, T., Sugiyama, Y. Transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II cell monolayer expressing both human organic anion-transporting polypeptide (OATP2/SLC21A6) and Multidrug resistance-associated protein 2 (MRP2/ABCC2). J Biol Chem 2002;277:6497-6503.
188. Matsushima, S., Maeda, K., Kondo, C., Hirano, M., Sasaki, M., Suzuki, H., Sugiyama, Y. Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J Pharmacol Exp Ther 2005;314:1059-1067.
189. Lowes, S., Simmons, N.L. Multiple pathways for fluoroquinolone secretion by human intestinal epithelial (Caco-2) cells. Br J Pharmacol 2002;135:1263-1275.
190. Bakos, E., Evers, R., Sinko, E., Varadi, A., Borst, P., Sarkadi, B. Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol Pharmacol 2000;57:760-768.
191. Kim, A.E., Dintaman, J.M., Waddell, D.S., Silverman, J.A. Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther 1998;286:1439-1445.
192. Liu, L., Cui, Y., Chung, A.Y., Shitara, Y., Sugiyama, Y., Keppler, D., Pang, K.S. (Vectorial Transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in rat and human livers. J Pharmacol Exp Ther 2006 (Epub ahead of print).
193. Spears, K.J., Ross, J., Stenhouse, A., Ward, C.J., Goh, L.B., Wolf, C.R., et al. Directional transepithelial transport of organic anions in porcine LLC-PK1 cells that co-express human OATP1B1 (OATP-C) and MRP2. Biochem Pharmacol 2005;69:415-423.
194. Guo, A., Marinaro, W., Hu, P., Sinko, P.J. Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos 2002;30:457-463.
195. Kiuchi, Y., Suzuki, H., Hirohashi, T., Tyson, C.A., Sugiyama, Y. cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett 1998;433:149-152.
196. Uchiumi, T., Hinoshita, E., Haga, S., Nakamura, T., Tanaka, T., Toh, S., et al. Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport. Biochem Biophys Res Commun 1998;252:103-110.
197. Zeng, H., Liu, G., Rea, P.A., Kruh, G.D. Transport of amphipathic anions by human multidrug resistance protein 3. Cancer Res 2000;60:4779-4784.
198. Inokuchi, A., Hinoshita, E., Iwamoto, Y., Kohno, K., Kuwano, M., Uchiumi, T. Enhanced expression of the human multidrug resistance protein 3 by bile salt in human enterocytes. A transcriptional control of a plausible bile acid transporter. J Biol Chem 2001;276:46822-46829.
199. Belinsky, M.G., Dawson, P.A., Shchaveleva, I., Bain, L.J., Wang, R., Ling, V., et al. Analysis of the in vivo functions of Mrp3. Mol Pharmacol 2005;68:160-168.
200. Zelcer, N., Saeki, T., Reid, G., Beijnen, J.H., Borst, P. Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem 2001;276:46400-46407.
201. Krishnamurthy, P., Schuetz, J.D. Role of ABCG2/BCRP in biology and medicine. Annu Rev Pharmacol Toxicol 2006;46:381-410.
202. Ifergan, I., Shafran, A., Jansen, G., Hooijberg, J.H., Scheffer, G.L., Assaraf, Y.G. Folate deprivation results in the loss of breast cancer resistance protein (BCRP/ABCG2) expression. A role for BCRP in cellular folate homeostasis. J Biol Chem 2004;279:25527-25534.
203. Sparreboom, A., Loos, W.J., Burger, H., Sissung, T.M., Verweij, J., Figg, W.D., et al. Effect of ABCG2 genotype on the oral bioavailability of topotecan. Cancer Biol Ther 2005;4:650-658.
204. 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;27:10-16.
205. Volk, E.L., Rohde, K., Rhee, M., McGuire, J.J., Doyle, L.A., Ross, D.D., Schneider, E. Methotrexate cross-resistance in a mitoxantrone-selected multidrug-resistant MCF7 breast cancer cell line is attributable to enhanced energy-dependent drug efflux. Cancer Res 2000;60:3514-3521.
206. Chen, Z.S., Robey, R.W., Belinsky, M.G., Shchaveleva, I., Ren, X.Q., Sugimoto, Y., et al. Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res 2003;63:4048-4054.
207. 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;64:610-618.
208. Candeil, L., Gourdier, I., Peyron, D., Vezzio, N., Copois, V., Bibeau, F., et al. ABCG2 overexpression in colon cancer cells resistant to SN38 and in irinotecan-treated metastases. Int J Cancer 2004;109:848-854.
209. Merino, G., Jonker, J.W., Wagenaar, E., van Herwaarden, A.E., Schinkel, A.H. The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin. Mol Pharmacol 2005;67:1758-1764.
210. 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;34:690-695.
211. Huang, L., Wang, Y., Grimm, S. ATP-dependent transport of rosuvastatin in membrane vesicles expressing breast cancer resistance protein. Drug Metab Dispos 2006;34:738-742.
212. Pavek, P., Merino, G., Wagenaar, E., Bolscher, E., Novotna, M., Jonker, J.W., Schinkel, A.H. Human breast cancer resistance protein: interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine. J Pharmacol Exp Ther 2005;312:144-152.
213. Merino, G., Jonker, J.W., Wagenaar, E., Pulido, M.M., Molina, A.J., Alvarez, A.I., Schinkel, A.H. Transport of anthelmintic benzimidazole drugs by breast cancer resistance protein (BCRP/ABCG2). Drug Metab Dispos 2005;33:614-618.
214. 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;67:923-928.
215. Zamber, C.P., Lamba, J.K., Yasuda, K., Farnum, J., Thummel, K., Schuetz, J.D., Schuetz, E.G. Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine. Pharmacogenetics 2003;13:19-28.
216. Sparreboom, A., Gelderblom, H., Marsh, S., Ahluwalia, R., Obach, R., Principe, P., et al. Diflomotecan pharmacokinetics in relation to ABCG2 421C. A genotype. Clin Pharmacol Ther 2004;76:38-44.
217. Henrich, C.J., Bokesch, H.R., Dean, M., Bates, S.E., Robey, R.W., Goncharova, E.I., et al. A highthroughput cell-based assay for inhibitors of ABCG2 activity. J Biomol Screen 2006;11:176-183.
218. Ji, Y., Morris, M.E. Effect of organic isothiocyanates on breast cancer resistance protein (ABCG2)-mediated transport. Pharm Res 2004;21:2261-2269.
219. Zhang, S., Wang, X., Sagawa, K., Morris, M.E. Flavonoids chrysin and benzoflavone, potent breast cancer resistance protein inhibitors, have no significant effect on topotecan pharmacokinetics in rats or mdr1a/1b(-/-) mice. Drug Metab Dispos 2005;33:341-348.
220. Zhang, S., Yang, X., Morris, M.E. Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Mol Pharmacol 2004;65:1208-1216.
221. Gupta, A., Zhang, Y., Unadkat, J.D., Mao, Q. HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther 2004;310:334-341.
222. Shiozawa, K., Oka, M., Soda, H., Yoshikawa, M., Ikegami, Y., Tsurutani, J., et al. Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic. Int J Cancer 2004;108:146-151.
223. Litman, T., Brangi, M., Hudson, E., Fetsch, P., Abati, A., Ross, D.D., et al. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 2000;113:2011-2021.
224. Maliepaard, M., van Gastelen, M.A., Tohgo, A., Hausheer, F.H., van Waardenburg, R.C., de Jong, L.A., et al. Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res 2001;7:935-941.
225. Burger, H., van Tol, H., Boersma, A.W., Brok, M., Wiemer, E.A., Stoter, G., Nooter, K. Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood 2004;104:2940-2942.
226. Nakanishi, T., Doyle, L.A., Hassel, B., Wei, Y., Bauer, K.S., Wu, S., et al. Functional characterization of human breast cancer resistance protein (BCRP, ABCG2) expressed in the oocytes of Xenopus laevis. Mol Pharmacol 2003;64:1452-1462.
227. Volk, E.L. Schneider, E. Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res 2003;63:5538-5543.
228. Schmitz, G., Langmann, T., Heimerl, S. Role of ABCG1 and other ABCG family members in lipid metabolism. J Lipid Res 2001;42:1513-1520.
229. Klett, E.L., Lee, M.H., Adams, D.B., Chavin, K.D., Patel, S.B. Localization of ABCG5 and ABCG8 proteins in human liver, gall bladder and intestine. BMC Gastroenterology 2004;21:4:21.
230. Repa, J.J., Berge, K.E., Pomajzl, C., Richardson, J.A., Hobbs, H., Mangelsdorf, D.J. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 2002;277:18793-18800.
231. Repa, J.J., Dietschy, J.M., Turley, S.D. Inhibition of cholesterol absorption by SCH 58053 in the mouse is not mediated via changes in the expression of mRNA for ABCA1, ABCG5, or ABCG8 in the enterocyte. J Lipid Res 2002;43:1864-1874.
232. Dieter, M.Z., Maher, J.M., Cheng, X., Klaassen, C.D. Expression and regulation of the sterol halftransporter genes ABCG5 and ABCG8 in rats. Comp Biochem Physiol C Toxicol Pharmacol 2004;139:209-221.
233. Zanlungo, S., Nervi, F. Discovery of the hepatic canalicular and intestinal cholesterol transporters. New targets for treatment of hypercholesterolemia. Eur Rev Med Pharmacol Sci 2003;7:33-39.
234. Geuken, E., Visser, D.S., Leuvenink, H.G., de Jong, K.P., Peeters, P.M., Slooff, M.J., et al. Hepatic expression of ABC transporters G5 and G8 does not correlate with biliary cholesterol secretion in liver transplant patients. Hepatology 2005;42:1166-1174.
235. Drobnik, W., Lindenthal, B., Lieser, B., Ritter, M., Christiansen Weber, T., Liebisch, G., et al. ATPbinding cassette transporter A1 (ABCA1) affects total body sterol metabolism. Gastroenterology 2001;120:1203-1211.
236. Oram, J.F., Heinecke, J.W. ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. Physiol Rev 2005;85:1343-1372.
237. Kaminski, W.E., Piehler, A., Wenzel, J.J. ABC A-subfamily transporters: Structure, function and disease. Biochim Biophys Acta 2006;1762:510-524.
238. Goldiner, I., van der Velde, A.E., Vandenberghe, K.E., van Wijland, M.A., Halpern, Z., Gilat, T., et al. ABCA1-dependent but ApoA-I-independent cholesterol efflux mediated by fatty acid-bile acid conjugates (FABACs). Biochem J 2006 [Epub ahead of print].
239. Tam, S.P., Mok, L., Chimini, G., Vasa, M., Deeley, R.G. ABCA1 mediates high-affinity uptake of 25-hydroxycholesterol by membrane vesicles and rapid efflux of the oxysterol by intact cells. Am J Physiol Cell Physiol 2006;Apr 12 [Epub ahead of print].
240. Takahashi, K., Kimura, Y., Kioka, N., Matsuo, M., Ueda, K. Purification and ATPase Activity of Human ABCA1. J Biol Chem 2006;281:10760-10768.
241. Frikke-Schmidt, R., Nordestgaard, B.G., Schnohr, P., Steffensen, R., Tybjaerg-Hansen, A. Mutation in ABCA1 predicted risk of ischemic heart disease in the Copenhagen City Heart Study Population. J Am Coll Cardiol 2005;46:1516-1520.
242. Charman, W. Lipids, Lipophilic Drugs, and Oral Drug Delivery-Some Emerging Concepts. J Pharm Sci 2000;89:967-978.
243. Khoo, S.M., Shackleford, D.M., Porter, C.J., Edwards, G.A., Charman, W.N. Intestinal lymphatic transport of halofantrine occurs after oral administration of a unit-dose lipid-based formulation to fasted dogs. Pharm Res 2003;20:1460-1465.
244. Lespine, A., Chanoit, G., Bousquet-Melou, A., Lallemand, E., Bassissi, F.M., Alvinerie, M., Toutain, P.L. Contribution of lymphatic transport to the systemic exposure of orally administered moxidectin in conscious lymph duct-cannulated dogs. Eur J Pharm Sci 2006;27:37-43.
245. Hugger, E.D., Novak, B.L., Burton, P.S., Audus, K.L., Borchardt, R.T. A comparison of commonly used polyethoxylated pharmaceutical excipients on their ability to inhibit P-glycoprotein activity in vitro. J Pharm Sci 2002;91:1991-2002.
246. Rege, B.D., Kao, J.P., Polli, J.E. Effects of nonionic surfactants on membrane transporters in Caco-2 cell monolayers. Eur J Pharm Sci 2002;16:237-246.
247. Lo, Y.L. Relationships between the hydrophilic-lipophilic balance values of pharmaceutical excipients and their multidrug resistance modulating effect in Caco-2 cells and rat intestines. J Control Release 2003;90:37-48.
248. Cornaire, G., Woodley, J.F., Saivin, S., Legendre, J.Y., Decourt, S., Cloarec, A., Houin, G. Effect of polyoxyl 35 castor oil and Polysorbate 80 on the intestinal absorption of digoxin in vitro. Arzneimittelforschung 2000;50:576-579.
249. Shono, Y., Nishihara, H., Matsuda, Y., Furukawa, S., Okada, N., Fujita, T., Yamamoto, A. Modulation of intestinal P-glycoprotein function by Cremophor EL and other surfactants by an in vitro diffusion chamber method using the isolated rat intestinal membranes. J Pharm Sci 2004;93:877-885.
250. Zhang, H., Yao, M., Morrison, R.A., Chong, S. Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats. Arch Pharm Res 2003;26:768-772.
251. Seeballuck, F., Ashford, M.B., O'Driscoll, C.M. The effects of pluronics block copolymers and Cremophor EL on intestinal lipoprotein processing and the potential link with P-glycoprotein in Caco-2 cells. Pharm Res 2003;20:1085-1092.
252. Cornaire, G., Woodley, J., Hermann, P., Cloarec, A., Arellano, C., Houin, G. Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo. Int J Pharm 2004;278:119-131.
253. Collnot, E.N., Baldes, C., Wempe, M.F., Hyatt, J., Navarro, L., Edgar, K.J., et al. Influence of vitamin E TPGS poly(ethylene glycol) chain length on apical efflux transporters in Caco-2 cell monolayers. J Control Release 2006;111:35-40.
254. Dintaman, J.M., Silverman, J.A. Inhibition of P-glycoprotein by D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Pharm Res 1999;16:1550-1556.
255. Hugger, E.D., Audus, K.L., Borchardt, R.T. Effects of poly(ethylene glycol) on efflux transporter activity in Caco-2 cell monolayers. J Pharm Sci 2002;91:1980-1990.
256. Batrakova, E.V., Li, S., Miller, D.W., Kabanov, A.V. Pluronic P85 increases permeability of a broad spectrum of drugs in polarized BBMEC and Caco-2 cell monolayers. Pharm Res 1999;16: 1366-1372.
257. Johnson, B.M., Charman, W.N., Porter, C.J. An in vitro examination of the impact of polyethylene glycol 400, Pluronic P85, and vitamin E d-alpha-tocopheryl polyethylene glycol 1000 succinate on P-glycoprotein efflux and enterocyte-based metabolism in excised rat intestine. AAPS Pharm Sci 2002;4:E40.
258. Regev, R., Assaraf, Y.G., Eytan, G.D. Membrane fluidization by ether, other anesthetics, and certain agents abolishes P-glycoprotein ATPase activity and modulates efflux from multidrug-resistant cells. Eur J Biochem 1999;259:18-24.
259. Lo, Y.L. Phospholipids as multidrug resistance modulators of the transport of epirubicin in human intestinal epithelial Caco-2 cell layers and everted gut sacs of rats. Biochem Pharmacol 2000;60:1381-1390.
260. Risovic, V., Sachs-Barrable, K., Boyd, M., Wasan, K.M. Potential mechanisms by which Peceol increases the gastrointestinal absorption of amphotericin, B. Drug Dev Ind Pharm 2004; 30:767-774.
261. Miller, D.W., Batrakova, E.V., Kabanov, A.V. Inhibition of multidrug resistance-associated protein (MRP) functional activity with pluronic block copolymers. Pharm Res 1999;16:396-401.
262. Kabanov, A.V., Batrakova, E.V., Alakhov, V.Y. An essential relationship between ATP depletion and chemosensitizing activity of Pluronic block copolymers. J Control Release 2003;91:75-83.
263. Batrakova, E.V., Li, S., Li, Y., Alakhov, V.Y., Kabanov, A.V. Effect of pluronic P85 on ATPase activity of drug efflux transporters. Pharm Res 2004;21:2226-2233.
264. Minko, T., Batrakova, E.V., Li, S., Li, Y., Pakunlu, R.I., Alakhov, V.Y., Kabanov, A.V. Pluronic block copolymers alter apoptotic signal transduction of doxorubicin in drug-resistant cancer cells. J Control Release 2005;105:269-278.
265. Kabanov, A.V., Batrakova, E.V., Alakhov, V.Y. Pluronic block copolymers for overcoming drug resistance in cancer. Adv Drug Deliv Rev 2002;54:759-779.
266. Yu, L., Bridgers, A., Polli, J., Vickers, A., Long, S., Roy, A., et al. Vitamin E-TPGS increases absorption flux of an HIV protease inhibitor by enhancing its solubility and permeability. Pharm Res 1999;16:812-1817.
267. Wong, H.L., Bendayan, R., Rauth, A.M., Xue, H.Y., Babakhanian, K., Wu, X.Y. A Mechanistic Study of enhanced doxorubicin uptake and retention in multidrug resistant breast cancer cells using a polymer-lipid hybrid nanoparticle (PLN) system. J Pharmacol Exp Ther 2006;Mar 17 [Epub ahead of print].