Hepatobiliary transporters in drug-induced cholestasis: a perspective on the current identifying tools

Bibliography

• Bleibel W, Kim S, D'Silva K, Lemmer ER. Drug-induced liver injury: review article. Dig Dis Sci 2007;52:2463-71
   PubMed Web of Science ®Google Scholar
• Kramer JA, Sagartz JE, Morris DL. The application of discovery toxicology and pathology towards the design of safer pharmaceutical lead candidates. Nat Rev Drug Discov 2007;6:636-49
   PubMed Web of Science ®Google Scholar
• Bell LN, Chalasani N. Epidemiology of idiosyncratic drug-induced liver injury. Semin Liver Dis 2009;29:337-47
   PubMed Web of Science ®Google Scholar
• Lee WM. Drug-induced acute liver failure. Clin Liver Dis 2013;17:575-86
   PubMed Web of Science ®Google Scholar
• Suzuki A, Andrade RJ, Bjornsson E, et al. Drugs associated with hepatotoxicity and their reporting frequency of liver adverse events in VigiBase: unified list based on international collaborative work. Drug Saf 2010;33:503-22
   PubMed Web of Science ®Google Scholar
• Ramachandran R, Kakar S. Histological patterns in drug-induced liver disease. J Clin Pathol 2009;62:481-92
   PubMed Web of Science ®Google Scholar
• Liss G, Lewis JH. Drug-induced liver injury: what was new in 2008? Expert Opin Drug Metab Toxicol 2009;5:843-60
   PubMed Web of Science ®Google Scholar
• Padda MS, Sanchez M, Akhtar AJ, Boyer JL. Drug-induced cholestasis. Hepatology 2011;53:1377-87
   PubMed Web of Science ®Google Scholar
• Bjornsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 2005;42:481-9
   PubMed Web of Science ®Google Scholar
• De Valle MB, Av Klinteberg V, Alem N, et al. Drug-induced liver injury in a swedish university hospital out-patient hepatology clinic. Aliment Pharmacol Ther 2006;24:1187-95
   PubMed Web of Science ®Google Scholar
• Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med 2006;354:731-9
   PubMed Web of Science ®Google Scholar
• Desmet VJ. Vanishing bile duct syndrome in drug-induced liver disease. J Hepatol 1997;26(Suppl 1):31-5
   PubMed Web of Science ®Google Scholar
• Kaplowitz N. Causality assessment versus guilt-by-association in drug hepatotoxicity. Hepatology 2001;33:308-10
   PubMed Web of Science ®Google Scholar
• Benichou C, Danan G, Flahault A. Causality assessment of adverse reactions to drugs--II. an original model for validation of drug causality assessment methods: case reports with positive rechallenge. J Clin Epidemiol 1993;46:1331-6
   PubMed Web of Science ®Google Scholar
• Danan G, Benichou C. Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993;46:1323-30
   PubMed Web of Science ®Google Scholar
• Rockey DC, Seeff LB, Rochon J, et al. Causality assessment in drug-induced liver injury using a structured expert opinion process: comparison to the roussel-uclaf causality assessment method. Hepatology 2010;51:2117-26
   PubMed Web of Science ®Google Scholar
• Esteller A. Physiology of bile secretion. World J Gastroenterol 2008;14:5641-9
   Google Scholar
• Hofmann AF. The enterohepatic circulation of bile acids in mammals: form and functions. Front Biosci 2009;14:2584-98
   PubMed Web of Science ®Google Scholar
• Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 2003;83:633-71
   PubMed Web of Science ®Google Scholar
• Dawson PA, Lan T, Rao A. Bile acid transporters. J Lipid Res 2009;50:2340-57
   PubMed Web of Science ®Google Scholar
• Monte MJ, Marin JJ, Antelo A, Vazquez-Tato J. Bile acids: chemistry, physiology, and pathophysiology. World J Gastroenterol 2009;15:804-16
   PubMed Web of Science ®Google Scholar
• Stahl S, Davies MR, Cook DI, Graham MJ. Nuclear hormone receptor-dependent regulation of hepatic transporters and their role in the adaptive response in cholestasis. Xenobiotica 2008;38:725-77
   PubMed Web of Science ®Google Scholar
• Alrefai WA, Gill RK. Bile acid transporters: structure, function, regulation and pathophysiological implications. Pharm Res 2007;24:1803-23
   PubMed Web of Science ®Google Scholar
• Eloranta JJ, Kullak-Ublick GA. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch Biochem Biophys 2005;433:397-412
   PubMed Web of Science ®Google Scholar
• Karpen SJ. Nuclear receptor regulation of hepatic function. J Hepatol 2002;36:832-50
   PubMed Web of Science ®Google Scholar
• Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 2004;126:322-42
   PubMed Web of Science ®Google Scholar
• Roth M, Obaidat A, Hagenbuch B. OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol 2012;165:1260-87
   PubMed Web of Science ®Google Scholar
• Borst P, Evers R, Kool M, Wijnholds J. A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 2000;92:1295-302
   PubMed Web of Science ®Google Scholar
• Alnouti Y. Bile acid sulfation: a pathway of bile acid elimination and detoxification. Toxicol Sci 2009;108:225-46
   PubMed Web of Science ®Google Scholar
• Nies AT, Keppler D. The apical conjugate efflux pump ABCC2 (MRP2). Pflugers Arch 2007;453:643-59
   PubMed Web of Science ®Google Scholar
• Geier A, Wagner M, Dietrich CG, Trauner M. Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration. Biochim Biophys Acta 2007;1773:283-308
   PubMed Web of Science ®Google Scholar
• Pauli-Magnus C, Meier PJ. Hepatobiliary transporters and drug-induced cholestasis. Hepatology 2006;44:778-87
   PubMed Web of Science ®Google Scholar
• Stieger B. The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) in physiology and pathophysiology of bile formation. Handb Exp Pharmacol 2011;201:205-59
   PubMedGoogle Scholar
• Lam P, Soroka CJ, Boyer JL. The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease. Semin Liver Dis 2010;30:125-33
   PubMed Web of Science ®Google Scholar
• Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis 2009;4:1
   PubMedGoogle Scholar
• van Erpecum KJ. Biliary lipids, water and cholesterol gallstones. Biol Cell 2005;97:815-22
   PubMed Web of Science ®Google Scholar
• Schneider G, Paus TC, Kullak-Ublick GA, et al. Linkage between a new splicing site mutation in the MDR3 alias ABCB4 gene and intrahepatic cholestasis of pregnancy. Hepatology 2007;45:150-8
   PubMed Web of Science ®Google Scholar
• Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. The spectrum of liver diseases related to ABCB4 gene mutations: pathophysiology and clinical aspects. Semin Liver Dis 2010;30:134-46
   PubMed Web of Science ®Google Scholar
• Small DM. Role of ABC transporters in secretion of cholesterol from liver into bile. Proc Natl Acad Sci USA 2003;100:4-6
   PubMed Web of Science ®Google Scholar
• Hazard SE, Patel SB. Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols. Pflugers Arch 2007;453:745-52
   PubMed Web of Science ®Google Scholar
• Trauner M, Fickert P, Halilbasic E, Moustafa T. Lessons from the toxic bile concept for the pathogenesis and treatment of cholestatic liver diseases. Wien Med Wochenschr 2008;158:542-8
   PubMedGoogle Scholar
• Borst P, Zelcer N, van de Wetering K, Poolman B. On the putative co-transport of drugs by multidrug resistance proteins. FEBS Lett 2006;580:1085-93
   PubMed Web of Science ®Google Scholar
• Kusuhara H, Sugiyama Y. ATP-binding cassette, subfamily G (ABCG family). Pflugers Arch 2007;453:735-44
   PubMed Web of Science ®Google Scholar
• Hagenbuch B, Meier PJ. Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch 2004;447:653-65
   PubMed Web of Science ®Google Scholar
• Ballatori N, Christian WV, Lee JY, et al. OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. Hepatology 2005;42:1270-9
   PubMed Web of Science ®Google Scholar
• Rost D, Konig J, Weiss G, et al. Expression and localization of the multidrug resistance proteins MRP2 and MRP3 in human gallbladder epithelia. Gastroenterology 2001;121:1203-8
   PubMed Web of Science ®Google Scholar
• Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov 2005;4:489-99
   PubMed Web of Science ®Google Scholar
• Campbell SD, de Morais SM, Xu JJ. Inhibition of human organic anion transporting polypeptide OATP 1B1 as a mechanism of drug-induced hyperbilirubinemia. Chem Biol Interact 2004;150:179-87
   PubMed Web of Science ®Google Scholar
• Chang JH, Plise E, Cheong J, et al. Evaluating the in vitro inhibition of UGT1A1, OATP1B1, OATP1B3, MRP2, and BSEP in predicting drug-induced hyperbilirubinemia. Mol Pharm 2013;10:3067-75
   PubMed Web of Science ®Google Scholar
• Chiou WJ, de Morais SM, Kikuchi R, et al. In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia. Xenobiotica 2013. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Sane R, Podila L, Mathur A, et al. In: Mechanisms of isolated unconjugated hyperbilirubinaemia induced by the HCV NS3/4A protease inhibitor BI 201335. EASL 46th Annual Meeting; 30th March - 3rd April 2011; Berlin, Germany
   Google Scholar
• Wlcek K, Koller F, Ferenci P, Stieger B. Hepatocellular organic anion-transporting polypeptides (OATPs) and multidrug resistance-associated protein 2 (MRP2) are inhibited by silibinin. Drug Metab Dispos 2013;41:1522-8
   PubMed Web of Science ®Google Scholar
• Byrne JA, Strautnieks SS, Mieli-Vergani G, et al. The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology 2002;123:1649-58
   PubMed Web of Science ®Google Scholar
• Noe J, Stieger B, Meier PJ. Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology 2002;123:1659-66
   PubMed Web of Science ®Google Scholar
• Stieger B, Fattinger K, Madon J, et al. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (bsep) of rat liver. Gastroenterology 2000;118:422-30
   PubMed Web of Science ®Google Scholar
• Fattinger K, Funk C, Pantze M, et al. The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther 2001;69:223-31
   PubMed Web of Science ®Google Scholar
• Kostrubsky VE, Strom SC, Hanson J, et al. Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats. Toxicol Sci 2003;76:220-8
   PubMed Web of Science ®Google Scholar
• Funk C, Ponelle C, Scheuermann G, Pantze M. Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: in vivo and in vitro interaction at the canalicular bile salt export pump (bsep) in the rat. Mol Pharmacol 2001;59:627-35
   PubMed Web of Science ®Google Scholar
• Dawson S, Stahl S, Paul N, et al. In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans. Drug Metab Dispos 2012;40:130-8
   PubMed Web of Science ®Google Scholar
• Morgan RE, Trauner M, van Staden CJ, et al. Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci 2010;118:485-500
   PubMed Web of Science ®Google Scholar
• Fouassier L, Kinnman N, Lefevre G, et al. Contribution of mrp2 in alterations of canalicular bile formation by the endothelin antagonist bosentan. J Hepatol 2002;37:184-91
   PubMed Web of Science ®Google Scholar
• Mano Y, Usui T, Kamimura H. Effects of bosentan, an endothelin receptor antagonist, on bile salt export pump and multidrug resistance-associated protein 2. Biopharm Drug Dispos 2007;28:13-18
   PubMed Web of Science ®Google Scholar
• Meier PJ. Canalicular bile formation: beyond single transporter functions. J Hepatol 2002;37:272-3
   PubMed Web of Science ®Google Scholar
• Ansede JH, Smith WR, Perry CH, et al. An in vitro assay to assess transporter-based cholestatic hepatotoxicity using sandwich-cultured rat hepatocytes. Drug Metab. Dispos 2010;38:276-80
   PubMed Web of Science ®Google Scholar
• Yoshikado T, Takada T, Yamamoto T, et al. Itraconazole-induced cholestasis: involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4. Mol Pharmacol 2011;79:241-50
   PubMed Web of Science ®Google Scholar
• Swift B, Pfeifer ND, Brouwer KL. Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity. Drug Metab Rev 2010;42:446-71
   PubMed Web of Science ®Google Scholar
• Thompson RA, Isin EM, Li Y, et al. Risk assessment and mitigation strategies for reactive metabolites in drug discovery and development. Chem Biol Interact 2011;192:65-71
   PubMed Web of Science ®Google Scholar
• Greer ML, Barber J, Eakins J, Kenna JG. Cell based approaches for evaluation of drug-induced liver injury. Toxicology 2010;268:125-31
   PubMed Web of Science ®Google Scholar
• Julie NL, Julie IM, Kende AI, Wilson GL. Mitochondrial dysfunction and delayed hepatotoxicity: another lesson from troglitazone. Diabetologia 2008;51:2108-16
   PubMed Web of Science ®Google Scholar
• Cosgrove BD, Alexopoulos LG, Saez-Rodriguez J, et al. A multipathway phosphoproteomic signaling network model of idiosyncratic drug- and inflammatory cytokine-induced toxicity in human hepatocytes. Conf Proc IEEE Eng Med Biol Soc 2009;2009:5452-5
   PubMedGoogle Scholar
• Roskmans TA, Desmet VJ. Drug-induced vanishing bile ducts syndromes. In: Alpini G, Alvaro D, Marzioni M, LeSage G, LaRusso N, editors, The pathophysiology of the biliary epithelia. Eurekah/Lendes Bioscience, Georgetown; 2004. p. 279-88
   Google Scholar
• Donaldson PT, Daly AK, Henderson J, et al. Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury. J Hepatol 2010;53:1049-53
   PubMed Web of Science ®Google Scholar
• Lucena MI, Molokhia M, Shen Y, et al. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology 2011;141:338-47
   PubMed Web of Science ®Google Scholar
• Pauli-Magnus C, Meier PJ. Pharmacogenetics of hepatocellular transporters. Pharmacogenetics 2003;13:189-98
   PubMedGoogle Scholar
• Kroetz DL, Pauli-Magnus C, Hodges LM, et al. Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics 2003;13:481-94
   PubMedGoogle Scholar
• Meier Y, Pauli-Magnus C, Zanger UM, et al. Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver. Hepatology 2006;44:62-74
   PubMed Web of Science ®Google Scholar
• Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2000;97:3473-8
   PubMed Web of Science ®Google Scholar
• Lang C, Meier Y, Stieger B, et al. Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury. Pharmacogenet Genomics 2007;17:47-60
   PubMed Web of Science ®Google Scholar
• Stieger B, Geier A. Genetic variations of bile salt transporters as predisposing factors for drug-induced cholestasis, intrahepatic cholestasis of pregnancy and therapeutic response of viral hepatitis. Expert Opin Drug Metab Toxicol 2011;7:411-25
   PubMed Web of Science ®Google Scholar
• Nicolaou M, Andress EJ, Zolnerciks JK, et al. Canalicular ABC transporters and liver disease. J Pathol 2012;226:300-15
   PubMed Web of Science ®Google Scholar
• Noe J, Kullak-Ublick GA, Jochum W, et al. Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis. J Hepatol 2005;43:536-43
   PubMed Web of Science ®Google Scholar
• Floreani A, Carderi I, Paternoster D, et al. Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations. Aliment Pharmacol Ther 2006;23:1649-53
   PubMed Web of Science ®Google Scholar
• Meier Y, Zodan T, Lang C, et al. Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump. World J Gastroenterol 2008;14:38-45
   PubMed Web of Science ®Google Scholar
• Dixon PH, van Mil SW, Chambers J, et al. Contribution of variant alleles of ABCB11 to susceptibility to intrahepatic cholestasis of pregnancy. Gut 2009;58:537-44
   PubMed Web of Science ®Google Scholar
• Ganne-Carrie N, Baussan C, Grando V, et al. Progressive familial intrahepatic cholestasis type 3 revealed by oral contraceptive pills. J Hepatol 2003;38:693-4
   PubMed Web of Science ®Google Scholar
• Niemi M, Pasanen MK, Neuvonen PJ. Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev 2011;63:157-81
   PubMed Web of Science ®Google Scholar
• Tirona RG, Leake BF, Merino G, Kim RB. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among european- and african-americans. J Biol Chem 2001;276:35669-75
   PubMed Web of Science ®Google Scholar
• Nozawa T, Minami H, Sugiura S, et al. Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. Drug Metab Dispos 2005;33:434-9
   PubMed Web of Science ®Google Scholar
• Niemi M. Transporter pharmacogenetics and statin toxicity. Clin Pharmacol Ther 2010;87:130-3
   PubMed Web of Science ®Google Scholar
• Ieiri I, Higuchi S, Sugiyama Y. Genetic polymorphisms of uptake (OATP1B1, 1B3) and efflux (MRP2, BCRP) transporters: implications for inter-individual differences in the pharmacokinetics and pharmacodynamics of statins and other clinically relevant drugs. Expert Opin Drug Metab Toxicol 2009;5:703-29
   PubMed Web of Science ®Google Scholar
• Franke RM, Gardner ER, Sparreboom A. Pharmacogenetics of drug transporters. Curr Pharm Des 2010;16:220-30
   PubMed Web of Science ®Google Scholar
• Fahrmayr C, Fromm MF, Konig J. Hepatic OATP and OCT uptake transporters: their role for drug-drug interactions and pharmacogenetic aspects. Drug Metab Rev 2010;42:380-401
   PubMed Web of Science ®Google Scholar
• van de Steeg E, Stranecky V, Hartmannova H, et al. Complete OATP1B1 and OATP1B3 deficiency causes human rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 2012;122:519-28
   PubMed Web of Science ®Google Scholar
• Ho RH, Tirona RG, Leake BF, et al. Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology 2006;130:1793-806
   PubMed Web of Science ®Google Scholar
• Smith DA, Schmid EF. Drug withdrawals and the lessons within. Curr Opin Drug Discov Devel 2006;9:38-46
   PubMed Web of Science ®Google Scholar
• Temple RJ, Himmel MH. Safety of newly approved drugs: implications for prescribing. JAMA 2002;287:2273-5
   PubMed Web of Science ®Google Scholar
• Kis E, Ioja E, Rajnai Z, et al. BSEP inhibition: in vitro screens to assess cholestatic potential of drugs. Toxicol in Vitro 2012;26:1294-9
   PubMed Web of Science ®Google Scholar
• Paulusma CC, de Waart DR, Kunne C, et al. Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content. J Biol Chem 2009;284:9947-54
   PubMed Web of Science ®Google Scholar
• Kis E, Ioja E, Nagy T, et al. Effect of membrane cholesterol on BSEP/bsep activity: species specificity studies for substrates and inhibitors. Drug Metab Dispos 2009;37:1878-86
   PubMed Web of Science ®Google Scholar
• Kis E, Rajnai Z, Ioja E, et al. Mouse bsep ATPase assay: a nonradioactive tool for assessment of the cholestatic potential of drugs. J Biomol Screen 2009;14:10-15
   PubMed Web of Science ®Google Scholar
• Asgari S, Pournasr B, Salekdeh GH, et al. Induced pluripotent stem cells: a new era for hepatology. J Hepatol 2010;53:738-51
   PubMed Web of Science ®Google Scholar
• Liu H, Ye Z, Kim Y, et al. Generation of endoderm-derived human induced pluripotent stem cells from primary hepatocytes. Hepatology 2010;51:1810-19
   PubMed Web of Science ®Google Scholar
• Wolf KK, Vora S, Webster LO, et al. Use of cassette dosing in sandwich-cultured rat and human hepatocytes to identify drugs that inhibit bile acid transport. Toxicol in Vitro 2010;24:297-309
   PubMed Web of Science ®Google Scholar
• Abe K, Bridges AS, Brouwer KL. Use of sandwich-cultured human hepatocytes to predict biliary clearance of angiotensin II receptor blockers and HMG-CoA reductase inhibitors. Drug Metab Dispos 2009;37:447-52
   PubMed Web of Science ®Google Scholar
• Nakakariya M, Ono M, Amano N, et al. In vivo biliary clearance should be predicted by intrinsic biliary clearance in sandwich-cultured hepatocytes. Drug Metab Dispos 2012;40:602-9
   PubMed Web of Science ®Google Scholar
• Mita S, Suzuki H, Akita H, et al. Vectorial transport of bile salts across MDCK cells expressing both rat na+-taurocholate cotransporting polypeptide and rat bile salt export pump. Am J Physiol Gastrointest Liver Physiol 2005;288:G159-67
   PubMed Web of Science ®Google Scholar
• Mita S, Suzuki H, Akita H, et al. Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat ntcp and bsep. Am J Physiol Gastrointest Liver Physiol 2006;290:G550-6
   PubMed Web of Science ®Google Scholar
• Xia CQ, Milton MN, Gan LS. Evaluation of drug-transporter interactions using in vitro and in vivo models. Curr Drug Metab 2007;8:341-63
   PubMed Web of Science ®Google Scholar
• Si-Tayeb K, Noto FK, Nagaoka M, et al. Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 2010;51:297-305
   PubMed Web of Science ®Google Scholar
• Seifinejad A, Tabebordbar M, Baharvand H, et al. Progress and promise towards safe induced pluripotent stem cells for therapy. Stem Cell. Rev 2010;6:297-306
   PubMed Web of Science ®Google Scholar
• Hay DC, Zhao D, Fletcher J, et al. Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo. Stem Cells 2008;26:894-902
   PubMed Web of Science ®Google Scholar
• Yamanaka S. A fresh look at iPS cells. Cell 2009;137:13-17
   PubMed Web of Science ®Google Scholar
• McRae MP, Lowe CM, Tian X, et al. Ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytes. J Pharmacol Exp Ther 2006;318:1068-75
   PubMed Web of Science ®Google Scholar
• Kostrubsky SE, Strom SC, Kalgutkar AS, et al. Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone. Toxicol Sci 2006;90:451-9
   PubMed Web of Science ®Google Scholar
• Green RM, Hoda F, Ward KL. Molecular cloning and characterization of the murine bile salt export pump. Gene 2000;241:117-23
   PubMed Web of Science ®Google Scholar
• Yabuuchi H, Tanaka K, Maeda M, et al. Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins. Biopharm Drug Dispos 2008;29:441-8
   PubMed Web of Science ®Google Scholar
• Hayashi H, Takada T, Suzuki H, et al. Transport by vesicles of glycine- and taurine-conjugated bile salts and taurolithocholate 3-sulfate: a comparison of human BSEP with rat bsep. Biochim Biophys Acta 2005;1738:54-62
   PubMed Web of Science ®Google Scholar
• Takekuma Y, Kakiuchi H, Yamazaki K, et al. Difference between pharmacokinetics of mycophenolic acid (MPA) in rats and that in humans is caused by different affinities of MRP2 to a glucuronized form. J Pharm Pharm Sci 2007;10:71-85
   PubMed Web of Science ®Google Scholar
• Li M, Yuan H, Li N, et al. Identification of interspecies difference in efflux transporters of hepatocytes from dog, rat, monkey and human. Eur J Pharm Sci 2008;35:114-26
   PubMed Web of Science ®Google Scholar
• Leslie EM, Watkins PB, Kim RB, Brouwer KL. Differential inhibition of rat and human na+-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1) by bosentan: a mechanism for species differences in hepatotoxicity. J Pharmacol Exp Ther 2007;321:1170-8
   PubMed Web of Science ®Google Scholar
• Jemnitz K, Veres Z, Vereczkey L. Contribution of high basolateral bile salt efflux to the lack of hepatotoxicity in rat in response to drugs inducing cholestasis in human. Toxicol Sci 2010;115:80-8
   PubMed Web of Science ®Google Scholar
• Wang R, Salem M, Yousef IM, et al. Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis. Proc Natl Acad Sci USA 2001;98:2011-16
   PubMed Web of Science ®Google Scholar
• Wang R, Lam P, Liu L, et al. Severe cholestasis induced by cholic acid feeding in knockout mice of sister of P-glycoprotein. Hepatology 2003;38:1489-99
   PubMed Web of Science ®Google Scholar
• Lam P, Wang R, Ling V. Bile acid transport in sister of P-glycoprotein (ABCB11) knockout mice. Biochemistry 2005;44:12598-605
   PubMed Web of Science ®Google Scholar
• Wang R, Chen HL, Liu L, et al. Compensatory role of P-glycoproteins in knockout mice lacking the bile salt export pump. Hepatology 2009;50:948-56
   PubMed Web of Science ®Google Scholar
• Saito H, Osumi M, Hirano H, et al. Technical pitfalls and improvements for high-speed screening and QSAR analysis to predict inhibitors of the human bile salt export pump (ABCB11/BSEP). AAPS J 2009;11:581-9
   PubMed Web of Science ®Google Scholar
• Warner DJ, Chen H, Cantin LD, et al. The inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification. Drug Metab Dispos 2012;40:2332-41
   PubMed Web of Science ®Google Scholar
• Keseru GM, Makara GM. The influence of lead discovery strategies on the properties of drug candidates. Nat Rev Drug Discov 2009;8:203-12
   PubMed Web of Science ®Google Scholar
• Feng S, He X. Mechanism-based inhibition of CYP450: an indicator of drug-induced hepatotoxicity. Curr Drug Metab 2013;14:921-45
   PubMed Web of Science ®Google Scholar
• Lammert C, Bjornsson E, Niklasson A, Chalasani N. Oral medications with significant hepatic metabolism at higher risk for hepatic adverse events. Hepatology 2010;51:615-20
   PubMed Web of Science ®Google Scholar
• FDA Working Group. PhRMA/FDA/AASLD Drug-induced hepatotoxicity White paper postmarketing considerations. FDA; Silver Spring, MD: 2000. Available from: http://www.fda.gov/downloads/Drugs/ScienceResearch/ResearchAreas/ucm091462.pdf [Last accessed 12 January 2014]
   Google Scholar
• Reuben A, Koch DG, Lee WM, Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010;52:2065-76
   PubMed Web of Science ®Google Scholar
• Watkins PB. Drug-induced liver injury network. Am J Gastroenterol 2008;103:1574-5
   PubMed Web of Science ®Google Scholar
• MedWatch: the FDA safety information and adverse event reporting program U.S. Food and Drug Administration. Available from: http://www.fda.gov/Safety/MedWatch/default.htm [Last accessed 12 January 2014]
   Google Scholar
• Graham DJ, Green L, Senior JR, Nourjah P. Troglitazone-induced liver failure: a case study. Am J Med 2003;114:299-306
   PubMed Web of Science ®Google Scholar
• Watkins PB. Insight into hepatotoxicity: the troglitazone experience. Hepatology 2005;41:229-30
   PubMed Web of Science ®Google Scholar
• Watkins PB, Whitcomb RW. Hepatic dysfunction associated with troglitazone. N Engl J Med 1998;338:916-17
   PubMed Web of Science ®Google Scholar
• Greupink R, Nabuurs SB, Zarzycka B, et al. In silico identification of potential cholestasis-inducing agents via modeling of na(+)-dependent taurocholate cotransporting polypeptide substrate specificity. Toxicol Sci 2012;129:35-48
   PubMed Web of Science ®Google Scholar
• Uehara T, Kiyosawa N, Shimizu T, et al. Species-specific differences in coumarin-induced hepatotoxicity as an example toxicogenomics-based approach to assessing risk of toxicity to humans. Hum Exp Toxicol 2008;27:23-35
   PubMed Web of Science ®Google Scholar