Role of membrane transporters in the safety profile of drugs Role of membrane transporters in the safety profile of drugs

Expert Opinion on Drug Metabolism and Toxicology

Volumn 5, Issue 11, 2009, Pages 1369-1383

  Lee, Edmund Jon Deoon ^a   Lean, Choo Bee ^a   Limenta, Lie Michael George ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

Distribution; Efficacy; Pharmacokinetics; Toxicity; Transporters

Indexed keywords

ABC TRANSPORTER; AMINO ACID TRANSPORTER; CARRIER PROTEIN; CYCLOSPORIN A; DEXAMETHASONE; DIGOXIN; DOXEPIN; GLYCOPROTEIN P; GREPAFLOXACIN; INDINAVIR; IVERMECTIN; MIRTAZAPINE; MONOCARBOXYLATE TRANSPORTER; MORPHINE; NELFINAVIR; OLANZAPINE; ORGANIC ANION TRANSPORTER; ORGANIC CATION TRANSPORTER; PAROXETINE; SAQUINAVIR; SLC TRANSPORTER; TACROLIMUS; UNCLASSIFIED DRUG; VENLAFAXINE; VINBLASTINE;

CELL MEMBRANE; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG EFFECT; DRUG EFFICACY; DRUG ELIMINATION; DRUG METABOLISM; DRUG PENETRATION; DRUG SAFETY; FOOD DRUG INTERACTION; HUMAN; MEMBRANE PERMEABILITY; MEMBRANE TRANSPORT; NERVE CELL MEMBRANE; NONHUMAN; PROTEIN EXPRESSION; REVIEW; TISSUE DISTRIBUTION;

ABSORPTION; AMINO ACID TRANSPORT SYSTEMS; ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; BRAIN; FOOD-DRUG INTERACTIONS; HUMANS; MEMBRANE TRANSPORT PROTEINS; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS; RNA, MESSENGER; SUBCELLULAR FRACTIONS; TISSUE DISTRIBUTION;

EID: 70449134221     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425250903176421     Document Type: Review

References (95)

1. Singer S, Nicholson G. The fluid mosaic model of the structure of cell membranes. Science NY 1972;175:720-731
2. Crane RK. Hypothesis for mechanism of intestinal active transport of sugars. Federation Proc 1962;21:891-895
3. Hediger MA, Ikeda T, Coady M, et al. Expression of size-selected mRNA encoding the intestinal Na/glucose cotransporter in Xenopus laevis oocytes. Proc Natl Acad Sci USA 1987;84(9):2634-2637
4. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 1976;455(1):152-162
5. Rees DC, Johnson E, Lewinson O. ABC transporters: the power to change. Nat Rev Mol Cell Biol 2009;10(3):218-227
6. Weiner JH, Furlong CE, Heppel LA. A binding protein for L-glutamine and its relation to active transport in E. coli. Arch Biochem Biophys 1971;142(2):715-717
7. Dean M, Annilo T. Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates [review]. Annu Rev Genomics Hum Genet 2005;6:123-142
8. Harland DN, Garmory HS, Brown KA, Titball RW. An association between ATP binding cassette systems, genome sizes and lifestyles of bacteria. Res Microbiol 2005;156(3):434-442
9. Gbelska Y, Krijger JJ, Breunig KD. Evolution of gene families: the multidrug resistance transporter genes in five related yeast species [review]. FEMS Yeast Res 2006;6(3):345-355
10. Gardner MJ, Hall N, Fung E, et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 2002;419(6906):498-511
11. Zutz A, Gompf S, Schägger H, Tampé R. Mitochondrial ABC proteins in health and disease. Biochim Biophys Acta 2009. [Epub ahead of print]
12. Sharom FJ, Liu R, Qu Q, Romsicki Y. Exploring the structure and function of the P-glycoprotein multidrug transporter using fluorescence spectroscopic tools. Semin Cell Dev Biol 2001;12(3):257-265
13. Pérez-Tomás R. Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. Curr Med Chem 2006;13(16):1859-1876
14. Fredriksson R, Nordström KJ, Stephansson O, et al. The solute carrier (SLC) complement of the human genome: phylogenetic classification reveals four major families. FEBS Lett 2008;582(27):3811-3816
15. He L, Vasiliou K, Nebert DW. Analysis and update of the human solute carrier (SLC) gene superfamily. Hum Genomics 2009;3(2):195-206
16. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46(1-3):3-26 (Pubitemid 33653411)
17. Dobson PD, Kell DB. Carrier-mediated cellular uptake of pharmaceutical drugs: An exception or the rule? Nat Rev Drug Discov 2008;7(3):205-220
18. Zimmermann C, Gutmann H, Hruz P, et al. Mapping of multidrug resistance gene 1 and multidrug resistance-associated protein isoform 1 to 5 mRNA expression along the human intestinal tract. Drug Metab Dispos 2005;33(2):219-224
19. Seithel A, Karlsson J, Hilgendorf C, et al. Variability in mRNA expression of ABC- and SLC-transporters in human intestinal cells: Comparison between human segments and Caco-2 cells. Eur J Pharm Sci 2006;28(4):291-299
20. Meier Y, Eloranta JJ, Darimont J, et al. Regional distribution of solute carrier mRNA expression along the human intestinal tract. Drug Metab Dispos 2007;35(4):590-594
21. Englund G, Rorsman F, Ronnblom A, et al. Regional levels of drug transporters along the human intestinal tract: Co-expression of ABC and SLC transporters and comparison with Caco-2 cells. Eur J Pharm Sci 2006;29(3-4):269-277
22. Hilgendorf C, Ahlin G, Seithel A, et al. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab Dispos 2007;35(8):1333-1340
23. Ji Y, Morris ME. Effect of organic isothiocyanates on breast cancer resistance protein (ABCG2)-mediated transport. Pharm Res 2004;21(12):2261-2269
24. Ji Y, Morris ME. Membrane transport of dietary phenethyl isothiocyanate by ABCG2 (breast cancer resistance protein). Mol Pharm 2005;2(5):414-419 (Pubitemid 41503682)
25. Bailey DG, Dresser GK, Leake BF, Kim RB. Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin Pharmacol Ther 2007;81(4):495-502
26. Shim CK, Cheon EP, Kang KW, et al. Inhibition effect of flavonoids on monocarboxylate transporter 1 (MCT1) in Caco-2 cells. J Pharm Pharmacol 2007;59(11):1515-1519
27. Nabekura T, Yamaki T, Kitagawa S. Effects of chemopreventive citrus phytochemicals on human P-glycoprotein and multidrug resistance protein 1. Eur J Pharmacol 2008;600(1-3):45-49
28. Nabekura T, Yamaki T, Ueno K, Kitagawa S. Effects of plant sterols on human multidrug transporters ABCB1 and ABCC1. Biochem Biophys Res Commun 2008;369(2):363-368
29. Wang X, Wolkoff AW, Morris ME. Flavonoids as a novel class of human organic anion-transporting polypeptide OATP1B1 (OATP-C) modulators. Drug Metab Dispos 2005;33(11):1666-1672
30. Wang X, Morris ME. Effects of the flavonoid chrysin on nitrofurantoin pharmacokinetics in rats: potential involvement of ABCG2. Drug Metab Dispos 2007;35(2):268-274
31. Williams RT. Detoxication Mechanisms. New York: John Wiley & Sons, Inc., 1959
32. Wilkinson GR. Clearance approaches in pharmacology [review]. Pharmacol Rev 1987;39(1):1-47
33. Petzinger E, Geyer J. Drug transporters in pharmacokinetics. Naunyn Schmiedebergs Arch Pharmacol 2006;372(6):465-475
34. Riley RJ, McGinnity DF, Austin RP. A unified model for predicting human hepatic, metabolic clearance from in vitro intrinsic clearance data in hepatocytes and microsomes. Drug Metab Dispos 2005;33(9):1304-1311
35. Brown HS, Griffin M, Houston JB. Evaluation of cryopreserved human hepatocytes as an alternative in vitro system to microsomes for the prediction of metabolic clearance. Drug Metab Dispos 2007;35(2):293-301
36. Hallifax D, Galetin A, Houston JB. Prediction of metabolic clearance using fresh human hepatocytes: Comparison with cryopreserved hepatocytes and hepatic microsomes for five benzodiazepines. Xenobiotica 2008;38(4):353-367
37. Shitara Y, Horie T, Sugiyama Y. Transporters as a determinant of drug clearance and tissue distribution [review]. Eur J Pharm Sci 2006;27(5):425-446
38. Funk C. The role of hepatic transporters in drug elimination [review]. Expert Opin Drug Metab Toxicol 2008;4(4):363-379
39. Szakács G, Váradi A, Ozvegy-Laczka C, Sarkadi B. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox) [review]. Drug Discov Today 2008;13(9-10):379-393
40. Smith HW, Goldring W, Chasis H. The measurement of the tubular excretory mass, effective blood flow and filtration rate in the normal human kidney. J Clin Invest 1938;17(3):263-278
41. Kinsella JL, Holohan PD, Pessah NI, Ross CR. Transport of organic ions in renal cortical luminal and antiluminal membrane vesicles. J Pharmacol Exp Ther 1979;209(3):443-450
42. Matsuzaki T, Morisaki T, Sugimoto W, et al. Altered pharmacokinetics of cationic drugs caused by down-regulation of renal rat organic cation transporter 2 (Slc22a2) and rat multidrug and toxin extrusion 1 (Slc47a1) in ischemia/reperfusion-induced acute kidney injury. Drug Metab Dispos 2008;36(4):649-654
43. Nowicki MT, Aleksunes LM, Sawant SP, et al. Renal and hepatic transporter expression in type 2 diabetic rats. Drug Metab Lett 2008;2(1):11-17
44. Warrington JS, Greenblatt DJ, von Moltke LL. The effect of age on P-glycoprotein expression and function in the Fischer-344 rat. J Pharmacol Exp Ther 2004;309(2):730-736
45. Gupta S. P-glycoprotein expression and regulation. Age-related changes and potential effects on drug therapy. Drugs Aging 1995;7(1):19-29
46. Grover A, Benet LZ. Effects of drug transporters on volume of distribution. AAPS J 2009;11(2):250-261
47. Ho RH, Kim RB. Transporters and drug therapy: Implications for drug disposition and disease. Clin Pharmacol Ther 2005;78(3):260-277
48. de Boer AG, van der Sandt IC, Gaillard PJ. The role of drug transporters at the blood-brain barrier. Annu Rev Pharmacol Toxicol 2003;43:629-656
49. Pardridge WM. Blood-brain barrier drug targeting: the future of brain drug development. Mol Interv 2003;3(2):90-105, 51
50. Youdim KA, Qaiser MZ, Begley DJ, et al. Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med 2004;36(5):592-604
51. Liu X, Tu M, Kelly RS, et al. Development of a computational approach to predict blood-brain barrier permeability. Drug Metab Dispos 2004;32(1):132-139
52. Summerfield SG, Read K, Begley DJ, et al. Central nervous system drug disposition: the relationship between in situ brain permeability and brain free fraction. J Pharmacol Exp Ther 2007;322(1):205-213
53. Hammarlund-Udenaes M, Friden M, Syvanen S, Gupta A. On the rate and extent of drug delivery to the brain. Pharm Res 2008;25(8):1737-1750
54. Kim RB, Fromm MF, Wandel C, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998;101(2):289-294
55. Sasongko L, Link JM, Muzi M, et al. Imaging P-glycoprotein transport activity at the human blood-brain barrier with positron emission tomography. Clin Pharmacol Ther 2005;77(6):503-514
56. Syvanen S, Lindhe O, Palner M, et al. Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport. Drug Metab Dispos 2009;37(3):635-643
57. Gould GW, Holman GD. The glucose transporter family: Structure, function and tissue-specific expression [review]. Biochem J 1993;295( Pt 2):329-341
58. Shayakul C, Hediger MA. The SLC14 gene family of urea transporters. Pflugers Arch 2004;447(5):603-609
59. Kobayashi D, Aizawa S, Maeda T, et al. Expression of organic cation transporter OCTN1 in hematopoietic cells during erythroid differentiation. Exp Hematol 2004;32(12):1156-1162
60. Endres CJ, Moss AM, Ke B, et al. The role of the equilibrative nucleoside transporter 1 (ENT1) in transport and metabolism of ribavirin by human and wild-type or Ent1-/- mouse erythrocytes. J Pharmacol Exp Ther 2009;329(1):387-398
61. Price NT, Jackson VN, Halestrap AP. Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past. Biochem J 1998;329(Pt 2):321-328
62. Köck K, Grube M, Jedlitschky G, et al. Expression of adenosine triphosphate-binding cassette (ABC) drug transporters in peripheral blood cells: relevance for physiology and pharmacotherapy [review]. Clin Pharmacokinet 2007;46(6):449-470
63. Available from: http://www.fda.gov/cder/ guidance/6695dft.pdf
64. Zhang L, Zhang YD, Strong JM, et al. A regulatory viewpoint on transporter-based drug interactions [review]. Xenobiotica 2008;38(7-8):709-724
65. Ikeguchi M. Water transport in aquaporins: Molecular dynamics simulations [review]. Front Biosci 2009;14:1283-1291
66. Agre P, Saboori AM, Asimos A, Smith BL. Purification and partial characterization of the Mr 30,000 integral membrane protein associated with the erythrocyte Rh(D) antigen. J Biol Chem 1987;262(36):17497-17503
67. Benga G. Water channel proteins (later called aquaporins) and relatives: past, present, and future. IUBMB Life 2009;61(2):112-133
68. Custodio JM, Wu CY, Benet LZ. Predicting drug disposition, absorption/ elimination/ transporter interplay and the role of food on drug absorption [review]. Adv Drug Deliv Rev 2008;60(6):717-733
69. Lin JH. Pharmacokinetic and pharmacodynamic variability: A daunting challenge in drug therapy. Curr Drug Metab 2007;8(2):109-136
70. Mather LE. Opioid pharmacokinetics in relation to their effects. Anaesth Intensive Care 1987;15(1):15-22
71. Roden DM, George AL Jr. The genetic basis of variability in drug responses. Nat Rev Drug Discov 2002;1(1):37-44
72. Petrovic V, Teng S, Piquette-Miller M. Regulation of drug transporters during infection and inflammation. Mol Interv 2007;7(2):99-111
73. Nolin TD, Naud J, Leblond FA, Pichette V. Emerging evidence of the impact of kidney disease on drug metabolism and transport. Clin Pharmacol Ther 2008;83(6):898-903
74. Lazarowski A, Czornyj L, Lubienieki F, et al. ABC transporters during epilepsy and mechanisms underlying multidrug resistance in refractory epilepsy. Epilepsia 2007;48(Suppl 5):140-149
75. Aszalos A. Drug-drug interactions affected by the transporter protein, P-glycoprotein (ABCB1, MDR1) II. Clinical aspects. Drug Discov Today 2007;12(19-20):838-843 (Pubitemid 47539962)
76. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: Mechanisms and clinical relevance. Clin Pharmacol Ther 2006;80(6):565-581
77. Morris ME, Zhang S. Flavonoid-drug interactions: Effects of flavonoids on ABC transporters. Life Sci 2006;78(18):2116-2130
78. Alvarez AI, Real R, Perez M, et al. Modulation of the activity of ABC transporters (P-glycoprotein, MRP2, BCRP) by flavonoids and drug response. J Pharm Sci 2009 [Epub ahead of print]
79. Deferme S, Augustijns P. The effect of food components on the absorption of P-gp substrates: A review. J Pharm Pharmacol 2003;55(2):153-162
80. Jones HM, Parrott N, Jorga K, Lave T. A novel strategy for physiologically based predictions of human pharmacokinetics. Clin Pharmacokinet 2006;45(5):511-542
81. Fenneteau F, Turgeon J, Couture L, et al. Assessing drug distribution in tissues expressing P-glycoprotein through physiologically based pharmacokinetic modeling: Model structure and parameters determination. Theor Biol Med Model 2009;6:2
82. Watanabe T, Kusuhara H, Maeda K, et al. Physiologically based pharmacokinetic modeling to predict transporter-mediated clearance and distribution of pravastatin in humans. J Pharmacol Exp Ther 2009;328(2):652-662
83. Huang SM, Strong JM, Zhang L, et al. New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process. J Clin Pharmacol 2008;48(6):662-670
84. Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute carrier transporter superfamilies. Drug Metab Pharmacokinet 2005;20(6):452-477
85. Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human solute carrier transporter superfamilies. Drug Metab Pharmacokinet 2008;23(1):22-44
86. Schinkel AH, Smit JJ, van Tellingen O, et al. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994;77(4):491-502
87. Schinkel AH, Wagenaar E, van Deemter L, et al. 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
88. Salama NN, Kelly EJ, Bui T, Ho RJ. The impact of pharmacologic and genetic knockout of P-glycoprotein on nelfinavir levels in the brain and other tissues in mice. J Pharm Sci 2005;94(6):1216-1225
89. Yamaguchi H, Yano I, Saito H, Inui K. Pharmacokinetic role of P-glycoprotein in oral bioavailability and intestinal secretion of grepafloxacin in vivo. J Pharmacol Exp Ther 2002;300(3):1063-1069
90. Wang JS, Taylor R, Ruan Y, et al. Olanzapine penetration into brain is greater in transgenic Abcb1a P-glycoprotein-deficient mice than FVB1 (wild-type) animals. Neuropsychopharmacology 2004;29(3):551-557
91. Yokogawa K, Takahashi M, Tamai I, et al. P-glycoprotein-dependent disposition kinetics of tacrolimus: Studies in mdr1a knockout mice. Pharm Res 1999;16(8):1213-1218
92. Uhr M, Grauer MT, Holsboer F. Differential enhancement of antidepressant penetration into the brain in mice with abcb1ab (mdr1ab) P-glycoprotein gene disruption. Biol Psychiatry 2003;54(8):840-846
93. Kawahara M, Sakata A, Miyashita T, et al. Physiologically based pharmacokinetics of digoxin in mdr1a knockout mice. J Pharm Sci 1999;88(12):1281-1287
94. Oswald S, Koll C, Siegmund W. Disposition of the cholesterol absorption inhibitor ezetimibe in mdr1a/b (-/-) mice. J Pharm Sci 2007;96(12):3478-3484
95. Kido Y, Tamai I, Ohnari A, et al. Functional relevance of carnitine transporter OCTN2 to brain distribution of L-carnitine and acetyl-L-carnitine across the blood-brain barrier. J Neurochem 2001;79(5):959-969