{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:03:52Z","timestamp":1790334232784,"version":"4.1.0"},"reference-count":36,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373938"],"award-info":[{"award-number":["82373938"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dmd.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Metabolism and Disposition"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.dmd.2026.100373","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:43:41Z","timestamp":1784331821000},"page":"100373","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic study on the species differences in metabolism and excretion pathways of ivarmacitinib between humans and rats"],"prefix":"10.1016","volume":"54","author":[{"given":"Xintong","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyu","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuandong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafang","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Diao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.dmd.2026.100373_bib1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1136\/ard-2024-226385","article-title":"Ivarmacitinib, a selective Janus kinase 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis and inadequate response to conventional synthetic DMARDs: results from a phase III randomised clinical trial","volume":"84","author":"Liu","year":"2025","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.dmd.2026.100373_bib2","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.biopha.2017.02.099","article-title":"Anti-arthritic effect of berberine on adjuvant-induced rheumatoid arthritis in rats","volume":"89","author":"Wang","year":"2017","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"10.1016\/j.dmd.2026.100373_bib3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/ard-2022-223356","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update","volume":"82","author":"Smolen","year":"2023","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"10.1016\/j.dmd.2026.100373_bib4","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s40265-017-0701-9","article-title":"JAK\u2013STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects","volume":"77","author":"Banerjee","year":"2017","journal-title":"Drugs"},{"key":"10.1016\/j.dmd.2026.100373_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2020.106210","article-title":"The role of JAK\/STAT signaling pathway and its inhibitors in diseases","volume":"80","author":"Xin","year":"2020","journal-title":"Int Immunopharmacol"},{"issue":"20","key":"10.1016\/j.dmd.2026.100373_bib6","doi-asserted-by":"crossref","first-page":"6690","DOI":"10.3390\/jcm12206690","article-title":"Janus kinase inhibitors in rheumatoid arthritis: an update on the efficacy and safety of tofacitinib, baricitinib and upadacitinib","volume":"12","author":"Harrington","year":"2023","journal-title":"J Clin Med"},{"issue":"4","key":"10.1016\/j.dmd.2026.100373_bib7","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.coph.2012.06.008","article-title":"Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease","volume":"12","author":"Kontzias","year":"2012","journal-title":"Curr Opin Pharmacol"},{"issue":"3","key":"10.1016\/j.dmd.2026.100373_bib8","doi-asserted-by":"crossref","first-page":"903","DOI":"10.3892\/ijmm.2016.2692","article-title":"Targeted blockade of JAK\/STAT3 signaling inhibits proliferation, migration and collagen production as well as inducing the apoptosis of hepatic stellate cells","volume":"38","author":"Gu","year":"2016","journal-title":"Int J Mol Med"},{"issue":"5","key":"10.1016\/j.dmd.2026.100373_bib9","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jbspin.2015.09.002","article-title":"JAK1-STAT3 blockade by JAK inhibitor SHR0302 attenuates inflammatory responses of adjuvant-induced arthritis rats and decreases Th17 and total B cells","volume":"83","author":"Wu","year":"2016","journal-title":"Joint Bone Spine"},{"issue":"12","key":"10.1016\/j.dmd.2026.100373_bib10","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1111\/bcp.15856","article-title":"Effect of SHR0302 on the pharmacokinetics of CYP3A4, CYP2C8, CYP2C9 and CYP2C19 probe substrates in healthy volunteers: a cocktail analysis","volume":"89","author":"Fu","year":"2023","journal-title":"Br J Clin Pharmacol"},{"issue":"2","key":"10.1016\/j.dmd.2026.100373_bib11","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/00498254.2023.2176267","article-title":"Mass balance study of [14C]SHR0302, a selective and potent JAK1 inhibitor in humans","volume":"53","author":"Ge","year":"2023","journal-title":"Xenobiotica"},{"issue":"9","key":"10.1016\/j.dmd.2026.100373_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.dmd.2025.100131","article-title":"Pharmacokinetics, mass balance, and metabolism of [14C]SAF-189s, a potent anaplastic lymphoma kinase\/c-ROS proto-oncogene 1 inhibitor in humans: metabolism potentially affected by interaction of cytochrome P450 enzymes and intestinal microbiota","volume":"53","author":"Yang","year":"2025","journal-title":"Drug Metab Dispos"},{"issue":"4","key":"10.1016\/j.dmd.2026.100373_bib13","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1124\/dmd.30.4.355","article-title":"Atypical kinetic profiles in drug metabolism reactions","volume":"30","author":"Hutzler","year":"2002","journal-title":"Drug Metab Dispos"},{"issue":"6","key":"10.1016\/j.dmd.2026.100373_bib14","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1124\/dmd.121.000581","article-title":"Pharmacokinetics, mass balance, and metabolism of the novel urate transporter 1 inhibitor [14C]HR011303 in humans: metabolism is mediated predominantly by UDP-glucuronosyltransferase","volume":"50","author":"Zheng","year":"2022","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.dmd.2026.100373_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2019.08.017","article-title":"Atypical Michaelis-Menten kinetics in cytochrome P450 enzymes: a focus on substrate inhibition","volume":"169","author":"Leow","year":"2019","journal-title":"Biochem Pharmacol"},{"issue":"10","key":"10.1016\/j.dmd.2026.100373_bib16","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1038\/s41401-020-0389-3","article-title":"Alflutinib (AST2818), primarily metabolized by CYP3A4, is a potent CYP3A4 inducer","volume":"41","author":"Liu","year":"2020","journal-title":"Acta Pharmacol Sin"},{"issue":"10","key":"10.1016\/j.dmd.2026.100373_bib17","doi-asserted-by":"crossref","first-page":"754","DOI":"10.2174\/0113892002351556250123105344","article-title":"In vitro and in vivo drug metabolism analysis of BPI-460372\u2014a covalent TEAD1\/3\/4 Inhibitor","volume":"25","author":"Liu","year":"2025","journal-title":"Curr Drug Metab"},{"issue":"5","key":"10.1016\/j.dmd.2026.100373_bib18","first-page":"465","article-title":"Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomes","volume":"57","author":"Rodrigues","year":"1999","journal-title":"Biochem Pharmacol"},{"issue":"7","key":"10.1016\/j.dmd.2026.100373_bib19","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1124\/dmd.31.7.815","article-title":"The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective","volume":"31","author":"Bjornsson","year":"2003","journal-title":"Drug Metab Dispos"},{"issue":"9","key":"10.1016\/j.dmd.2026.100373_bib20","doi-asserted-by":"crossref","first-page":"911","DOI":"10.2174\/138920008786485056","article-title":"Permeability--in vitro assays for assessing drug transporter activity","volume":"9","author":"Jin","year":"2008","journal-title":"Curr Drug Metab"},{"issue":"9","key":"10.1016\/j.dmd.2026.100373_bib21","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1080\/00498254.2018.1531158","article-title":"Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, in cynomolgus monkeys","volume":"49","author":"Nagai","year":"2019","journal-title":"Xenobiotica"},{"issue":"2","key":"10.1016\/j.dmd.2026.100373_bib22","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1021\/mp900227a","article-title":"Influence of seeding density and extracellular matrix on bile acid transport and Mrp4 expression in sandwich-cultured mouse hepatocytes","volume":"7","author":"Swift","year":"2010","journal-title":"Mol Pharm"},{"issue":"2","key":"10.1016\/j.dmd.2026.100373_bib23","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/toxsci\/kfr014","article-title":"Differential disposition of chenodeoxycholic acid versus taurocholic acid in response to acute troglitazone exposure in rat hepatocytes","volume":"120","author":"Marion","year":"2011","journal-title":"Toxicol Sci"},{"key":"10.1016\/j.dmd.2026.100373_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2021.120125","article-title":"Site-specific protein modification by 3-n-butylphthalide in primary hepatocytes: covalent protein adducts diminished by glutathione and N-acetylcysteine","volume":"287","author":"Xue","year":"2021","journal-title":"Life Sci"},{"issue":"6","key":"10.1016\/j.dmd.2026.100373_bib25","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1124\/dmd.121.000582","article-title":"Mechanistic study on the species differences in excretion pathway of HR011303 in humans and rats","volume":"50","author":"Guo","year":"2022","journal-title":"Drug Metab Dispos"},{"issue":"5","key":"10.1016\/j.dmd.2026.100373_bib26","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1002\/jps.23070","article-title":"Assessment of biliary clearance in early drug discovery using sandwich-cultured hepatocyte model","volume":"101","author":"Pan","year":"2012","journal-title":"J Pharm Sci"},{"issue":"5","key":"10.1016\/j.dmd.2026.100373_bib27","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1124\/dmd.114.062000","article-title":"Renal tubular secretion of tanshinol: molecular mechanisms, impact on its systemic exposure, and propensity for dose-related nephrotoxicity and for renal herb-drug interactions","volume":"43","author":"Jia","year":"2015","journal-title":"Drug Metab Dispos"},{"issue":"4","key":"10.1016\/j.dmd.2026.100373_bib28","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1111\/bph.12971","article-title":"Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb\u2013drug interactions on OATP1B3","volume":"172","author":"Jiang","year":"2015","journal-title":"Br J Pharmacol"},{"issue":"5","key":"10.1016\/j.dmd.2026.100373_bib29","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1208\/s12248-020-00501-9","article-title":"Investigating the theoretical basis for in vitro-in vivo extrapolation (IVIVE) in predicting drug metabolic clearance and proposing future experimental pathways","volume":"22","author":"Benet","year":"2020","journal-title":"AAPS J"},{"issue":"2","key":"10.1016\/j.dmd.2026.100373_bib30","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1124\/dmd.112.049684","article-title":"Metabolism and pharmacokinetics of 3-n-butylphthalide (NBP) in humans: the role of cytochrome P450s and alcohol dehydrogenase in biotransformation","volume":"41","author":"Diao","year":"2013","journal-title":"Drug Metab Dispos"},{"issue":"7","key":"10.1016\/j.dmd.2026.100373_bib31","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1023\/A:1018943613122","article-title":"Physiological parameters in laboratory animals and humans","volume":"10","author":"Davies","year":"1993","journal-title":"Pharm Res"},{"issue":"8","key":"10.1016\/j.dmd.2026.100373_bib32","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.tiv.2006.06.003","article-title":"Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements","volume":"20","author":"Sohlenius-Sternbeck","year":"2006","journal-title":"Toxicol In Vitro"},{"issue":"8","key":"10.1016\/j.dmd.2026.100373_bib33","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1111\/bcp.15733","article-title":"Effect of CYP3A4 induction and inhibition on the pharmacokinetics of SHR0302 in healthy subjects","volume":"89","author":"Zhang","year":"2023","journal-title":"Br J Clin Pharmacol"},{"issue":"12","key":"10.1016\/j.dmd.2026.100373_bib34","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1080\/00498250010021684","article-title":"Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man","volume":"30","author":"Bogaards","year":"2000","journal-title":"Xenobiotica"},{"issue":"2","key":"10.1016\/j.dmd.2026.100373_bib35","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1582-4934.2002.tb00186.x","article-title":"Cytochromes P450 and experimental models of drug metabolism","volume":"6","author":"Zuber","year":"2002","journal-title":"J Cell Mol Med"},{"issue":"6","key":"10.1016\/j.dmd.2026.100373_bib36","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1517\/17425255.2.6.875","article-title":"Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction","volume":"2","author":"Martignoni","year":"2006","journal-title":"Expert Opin Drug Metab Toxicol"}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955626006422?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955626006422?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:17:06Z","timestamp":1790331426000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955626006422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S0090955626006422"],"URL":"https:\/\/doi.org\/10.1016\/j.dmd.2026.100373","relation":{},"ISSN":["0090-9556"],"issn-type":[{"value":"0090-9556","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mechanistic study on the species differences in metabolism and excretion pathways of ivarmacitinib between humans and rats","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.dmd.2026.100373","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"100373"}}