{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:56:30Z","timestamp":1791982590726,"version":"4.4.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["dmd.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Metabolism and Disposition"],"published-print":{"date-parts":[[2015,11]]},"DOI":"10.1124\/dmd.115.065425","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T01:23:51Z","timestamp":1441157031000},"page":"1760-1768","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":42,"title":["Prediction of the Clinical Risk of Drug-Induced Cholestatic Liver Injury Using an In Vitro Sandwich Cultured Hepatocyte Assay"],"prefix":"10.1016","volume":"43","author":[{"given":"Takeshi","family":"Susukida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Sekine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuka","family":"Nozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuko","family":"Tokizono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousei","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/dmd.115.065425_bib1","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/hep.27206","article-title":"Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump","volume":"60","author":"Aleo","year":"2014","journal-title":"Hepatology"},{"key":"10.1124\/dmd.115.065425_bib2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1055\/s-0034-1375961","article-title":"DILI and drug development: a regulatory perspective","volume":"34","author":"Avigan","year":"2014","journal-title":"Semin Liver Dis"},{"key":"10.1124\/dmd.115.065425_bib3","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1124\/dmd.109.027482","article-title":"Investigation of the influence of CYP1A2 and CYP2C19 genetic polymorphism on 2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide (A77 1726) pharmacokinetics in leflunomide-treated patients with rheumatoid arthritis","volume":"37","author":"Bohanec Grabar","year":"2009","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.115.065425_bib4","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1053\/gast.2002.36591","article-title":"The human bile salt export pump: characterization of substrate specificity and identification of inhibitors","volume":"123","author":"Byrne","year":"2002","journal-title":"Gastroenterology"},{"key":"10.1124\/dmd.115.065425_bib5","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/ajg.2014.131","article-title":"ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury","volume":"109","author":"Chalasani","year":"2014","journal-title":"Am J Gastroenterol"},{"key":"10.1124\/dmd.115.065425_bib6","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1124\/dmd.111.040758","article-title":"In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans","volume":"40","author":"Dawson","year":"2012","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.115.065425_bib7","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1177\/0091270009343005","article-title":"Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans","volume":"50","author":"Farid","year":"2010","journal-title":"J Clin Pharmacol"},{"key":"10.1124\/dmd.115.065425_bib8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1067\/mcp.2001.114667","article-title":"The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions","volume":"69","author":"Fattinger","year":"2001","journal-title":"Clin Pharmacol Ther"},{"key":"10.1124\/dmd.115.065425_bib9","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0300-483X(01)00460-7","volume":"167","author":"Funk","year":"2001","journal-title":"Toxicology"},{"key":"10.1124\/dmd.115.065425_bib10","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1124\/dmd.108.021055","article-title":"Functional consequences of active hepatic uptake on cytochrome P450 inhibition in rat and human hepatocytes","volume":"36","author":"Grime","year":"2008","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.115.065425_bib11","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/clpt.1990.207","article-title":"The influence of age and gender on the stereoselective metabolism and pharmacokinetics of mephobarbital in humans","volume":"48","author":"Hooper","year":"1990","journal-title":"Clin Pharmacol Ther"},{"key":"10.1124\/dmd.115.065425_bib12","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1042\/bj3270305","article-title":"ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2","volume":"327","author":"Jedlitschky","year":"1997","journal-title":"Biochem J"},{"key":"10.1124\/dmd.115.065425_bib13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/hep.26295","article-title":"Avoiding idiosyncratic DILI: two is better than one","volume":"58","author":"Kaplowitz","year":"2013","journal-title":"Hepatology"},{"key":"10.1124\/dmd.115.065425_bib14","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1097\/01.fpc.0000114764.78957.22","article-title":"Pharmacogenetic roles of CYP2C19 and CYP2B6 in the metabolism of R- and S-mephobarbital in humans","volume":"14","author":"Kobayashi","year":"2004","journal-title":"Pharmacogenetics"},{"key":"10.1124\/dmd.115.065425_bib15","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1124\/dmd.113.054304","article-title":"Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters multidrug resistance-associated proteins 3 and 4","volume":"42","author":"K\u00f6ck","year":"2014","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.115.065425_bib16","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/toxsci\/kfj095","article-title":"Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone","volume":"90","author":"Kostrubsky","year":"2006","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.115.065425_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2012.02.002","article-title":"Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes","volume":"261","author":"Marion","year":"2012","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.115.065425_bib18","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.physiol.64.082201.100300","article-title":"Bile salt transporters","volume":"64","author":"Meier","year":"2002","journal-title":"Annu Rev Physiol"},{"key":"10.1124\/dmd.115.065425_bib19","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/toxsci\/kfq269","article-title":"Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development","volume":"118","author":"Morgan","year":"2010","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.115.065425_bib20","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1093\/toxsci\/kft176","article-title":"A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development","volume":"136","author":"Morgan","year":"2013","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.115.065425_bib21","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.dmpk.2015.05.003","article-title":"The impact of genetic polymorphisms of drug metabolizing enzymes on the pharmacodynamics of clopidogrel under steady state conditions","volume":"30","author":"Nakkam","year":"2015","journal-title":"Drug Metab Pharmacokinet"},{"key":"10.1124\/dmd.115.065425_bib22","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bbrc.2011.11.032","article-title":"Bile salt export pump inhibitors are associated with bile acid-dependent drug-induced toxicity in sandwich-cultured hepatocytes","volume":"416","author":"Ogimura","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1124\/dmd.115.065425_bib23","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/toxsci\/kft197","article-title":"Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP\/ABCB11)","volume":"136","author":"Pedersen","year":"2013","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.115.065425_bib24","doi-asserted-by":"crossref","first-page":"164","DOI":"10.4172\/2155-9872.1000164","article-title":"Differences and similarities in the metabolism of glyburide for various species: an analysis by LC-DAD-Q-TRAP-MS\/MS","volume":"4","author":"Ravindran","year":"2013","journal-title":"J Anal Bioanal Tech"},{"key":"10.1124\/dmd.115.065425_bib25","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/toxsci\/71.2.276","article-title":"Cyclosporin A induced internalization of the bile salt export pump in isolated rat hepatocyte couplets","volume":"71","author":"Roman","year":"2003","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.115.065425_bib26","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1016\/j.jchromb.2009.09.038","article-title":"Rapid quantification of bile acids and their conjugates in serum by liquid chromatography-tandem mass spectrometry","volume":"877","author":"Scherer","year":"2009","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"10.1124\/dmd.115.065425_bib27","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0016-5085(00)70224-1","article-title":"Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver","volume":"118","author":"Stieger","year":"2000","journal-title":"Gastroenterology"},{"key":"10.1124\/dmd.115.065425_bib28","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/3034","article-title":"A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis","volume":"20","author":"Strautnieks","year":"1998","journal-title":"Nat Genet"},{"key":"10.1124\/dmd.115.065425_bib29","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/j.tiv.2015.06.004","article-title":"Basal efflux of bile acids contributes to drug-induced bile acid-dependent hepatocyte toxicity in rat sandwich-cultured hepatocytes","volume":"29","author":"Susukida","year":"2015","journal-title":"Toxicol In Vitro"},{"key":"10.1124\/dmd.115.065425_bib30","doi-asserted-by":"crossref","first-page":"446","DOI":"10.3109\/03602530903491881","article-title":"Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity","volume":"42","author":"Swift","year":"2010","journal-title":"Drug Metab Rev"},{"key":"10.1124\/dmd.115.065425_bib31","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nrd2619","article-title":"Targeting bile-acid signalling for metabolic diseases","volume":"7","author":"Thomas","year":"2008","journal-title":"Nat Rev Drug Discov"},{"key":"10.1124\/dmd.115.065425_bib32","first-page":"513","article-title":"Early alteration in bone metabolism in epileptic children receiving carbamazepine monotherapy owing to the induction of hepatic drug-metabolizing enzymes","volume":"20","author":"Voudris","year":"2005","journal-title":"J Child Neurol"},{"key":"10.1124\/dmd.115.065425_bib33","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1002\/hep.23089","article-title":"Compensatory role of P-glycoproteins in knockout mice lacking the bile salt export pump","volume":"50","author":"Wang","year":"2009","journal-title":"Hepatology"},{"key":"10.1124\/dmd.115.065425_bib34","first-page":"1489","article-title":"Severe cholestasis induced by cholic acid feeding in knockout mice of sister of P-glycoprotein","volume":"38","author":"Wang","year":"2003","journal-title":"Hepatology"},{"key":"10.1124\/dmd.115.065425_bib35","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1124\/dmd.112.047068","article-title":"Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification","volume":"40","author":"Warner","year":"2012","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.115.065425_bib36","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.3748\/wjg.v18.i36.4985","article-title":"Novel insight into mechanisms of cholestatic liver injury","volume":"18","author":"Woolbright","year":"2012","journal-title":"World J Gastroenterol"},{"key":"10.1124\/dmd.115.065425_bib37","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1124\/dmd.114.057190","article-title":"Hepatocellular exposure of troglitazone metabolites in rat sandwich-cultured hepatocytes lacking Bcrp and Mrp2: interplay between formation and excretion","volume":"42","author":"Yang","year":"2014","journal-title":"Drug Metab Dispos"}],"updated-by":[{"DOI":"10.1124\/dmd.112.065425err","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000}}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624102231?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624102231?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/dmd.115.065425","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T19:24:58Z","timestamp":1739906698000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955624102231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11]]},"references-count":37,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["S0090955624102231"],"URL":"https:\/\/doi.org\/10.1124\/dmd.115.065425","relation":{},"ISSN":["0090-9556"],"issn-type":[{"value":"0090-9556","type":"print"}],"subject":[],"published":{"date-parts":[[2015,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Prediction of the Clinical Risk of Drug-Induced Cholestatic Liver Injury Using an In Vitro Sandwich Cultured Hepatocyte Assay","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/dmd.115.065425","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2015 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}