{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:38:06Z","timestamp":1773934686344,"version":"3.50.1"},"reference-count":44,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100017688","name":"Guangdong Provincial Key Laboratory of Construction Foundation","doi-asserted-by":"publisher","award":["2017B030314030"],"award-info":[{"award-number":["2017B030314030"]}],"id":[{"id":"10.13039\/501100017688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017688","name":"Guangdong Provincial Key Laboratory of Construction Foundation","doi-asserted-by":"publisher","award":["2020B1212060034"],"award-info":[{"award-number":["2020B1212060034"]}],"id":[{"id":"10.13039\/501100017688","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":[[2025,12]]},"DOI":"10.1016\/j.dmd.2025.100126","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T15:56:54Z","timestamp":1753286214000},"page":"100126","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic changes of nintedanib in collagen-induced arthritic rats are related to reduction of intestinal P-glycoprotein expression"],"prefix":"10.1016","volume":"53","author":[{"given":"Gengyi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyan","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaokun","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangqing","family":"Ning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.dmd.2025.100126_bib1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/annrheumdis-2015-207524","article-title":"Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force","volume":"75","author":"Smolen","year":"2016","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"10.1016\/j.dmd.2025.100126_bib2","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1136\/ard.2010.138693","article-title":"Physical disability in rheumatoid arthritis is associated with cartilage damage rather than bone destruction","volume":"70","author":"Aletaha","year":"2011","journal-title":"Ann Rheum Dis"},{"issue":"7","key":"10.1016\/j.dmd.2025.100126_bib3","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nm.3260","article-title":"How cytokine networks fuel inflammation: toward a cytokine-based disease taxonomy","volume":"19","author":"Schett","year":"2013","journal-title":"Nat Med"},{"issue":"9","key":"10.1016\/j.dmd.2025.100126_bib4","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1136\/annrheumdis-2011-200726","article-title":"Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies","volume":"71","author":"Avina-Zubieta","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.dmd.2025.100126_bib5","article-title":"Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications","volume":"361","author":"England","year":"2018","journal-title":"BMJ"},{"issue":"2","key":"10.1016\/j.dmd.2025.100126_bib6","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s10067-010-1492-5","article-title":"Pulmonary involvement in early rheumatoid arthritis patients","volume":"30","author":"Habib","year":"2011","journal-title":"Clin Rheumatol"},{"issue":"10086","key":"10.1016\/j.dmd.2025.100126_bib7","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1016\/S0140-6736(17)31472-1","article-title":"Pathogenetic insights from the treatment of rheumatoid arthritis","volume":"389","author":"McInnes","year":"2017","journal-title":"Lancet"},{"issue":"7","key":"10.1016\/j.dmd.2025.100126_bib8","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1021\/acs.molpharmaceut.2c00140","article-title":"TNF-\u03b1 and IL-1\u03b2 exposure modulates the expression and functionality of P-glycoprotein in intestinal and renal barriers","volume":"19","author":"Saib","year":"2022","journal-title":"Mol Pharm"},{"issue":"18","key":"10.1016\/j.dmd.2025.100126_bib9","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1056\/NEJMoa1908681","article-title":"Nintedanib in progressive fibrosing interstitial lung diseases","volume":"381","author":"Flaherty","year":"2019","journal-title":"N Engl J Med"},{"issue":"14","key":"10.1016\/j.dmd.2025.100126_bib10","doi-asserted-by":"crossref","first-page":"4466","DOI":"10.1021\/jm900431g","article-title":"Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120)","volume":"52","author":"Roth","year":"2009","journal-title":"J Med Chem"},{"issue":"9","key":"10.1016\/j.dmd.2025.100126_bib11","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1002\/art.40904","article-title":"Rheumatoid arthritis disease activity predicting incident clinically apparent rheumatoid arthritis-associated interstitial lung disease: a prospective cohort study","volume":"71","author":"Sparks","year":"2019","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"10.1016\/j.dmd.2025.100126_bib12","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-72768-z","article-title":"A prospective study of lung disease in a cohort of early rheumatoid arthritis patients","volume":"10","author":"Robles-P\u00e9rez","year":"2020","journal-title":"Sci Rep"},{"issue":"6","key":"10.1016\/j.dmd.2025.100126_bib14","doi-asserted-by":"crossref","first-page":"L998","DOI":"10.1152\/ajplung.00304.2017","article-title":"Nintedanib reduces pulmonary fibrosis in a model of rheumatoid arthritis-associated interstitial lung disease","volume":"314","author":"Redente","year":"2018","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.dmd.2025.100126_bib15","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2147\/DDDT.S284819","article-title":"Clinical significance of continuable treatment with nintedanib over 12 months for idiopathic pulmonary fibrosis in a real-world setting","volume":"15","author":"Kato","year":"2021","journal-title":"Drug Des Dev Ther"},{"issue":"12","key":"10.1016\/j.dmd.2025.100126_bib16","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1093\/rheumatology\/keaa503","article-title":"Nintedanib for the treatment of refractory progressive rheumatoid arthritis-related interstitial lung disease: a real-life case series","volume":"59","author":"Narv\u00e1ez","year":"2020","journal-title":"Rheumatology (Oxford)"},{"issue":"12","key":"10.1016\/j.dmd.2025.100126_bib17","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s11926-024-01155-8","article-title":"Rheumatoid arthritis-associated interstitial lung disease (RA-ILD): update on prevalence, risk factors, pathogenesis, and therapy","volume":"26","author":"Sullivan","year":"2024","journal-title":"Curr Rheumatol Rep"},{"issue":"4","key":"10.1016\/j.dmd.2025.100126_bib18","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1007\/s12325-022-02411-y","article-title":"Real-world safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: interim report of a post-marketing surveillance in Japan","volume":"40","author":"Ogura","year":"2023","journal-title":"Adv Ther"},{"issue":"1","key":"10.1016\/j.dmd.2025.100126_bib19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12931-018-0907-8","article-title":"Efficacy and safety of nintedanib in advanced idiopathic pulmonary fibrosis","volume":"19","author":"Yoon","year":"2018","journal-title":"Respir Res"},{"issue":"10","key":"10.1016\/j.dmd.2025.100126_bib20","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1002\/art.40574","article-title":"The lung in rheumatoid arthritis: focus on interstitial lung disease","volume":"70","author":"Spagnolo","year":"2018","journal-title":"Arthritis Rheumatol"},{"issue":"5","key":"10.1016\/j.dmd.2025.100126_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.autrev.2022.103056","article-title":"Pathogenesis, clinical features, and treatment strategy for rheumatoid arthritis-associated interstitial lung disease","volume":"21","author":"Akiyama","year":"2022","journal-title":"Autoimmun Rev"},{"key":"10.1016\/j.dmd.2025.100126_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.116782","article-title":"Effect of Salvia miltiorrhiza Bunge extracts on improving the efficacy and reducing the toxicity of Tripterygium wilfordii polyglycosides in the treatment of rheumatoid arthritis","volume":"317","author":"Zhang","year":"2023","journal-title":"J Ethnopharmacol"},{"key":"10.1016\/j.dmd.2025.100126_bib24","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1215364","article-title":"The role of interleukin-18 and interleukin-18 binding protein in K\/BxN serum transfer-induced arthritis","volume":"14","author":"Fauteux-Daniel","year":"2023","journal-title":"Front Immunol"},{"issue":"1","key":"10.1016\/j.dmd.2025.100126_bib25","doi-asserted-by":"crossref","first-page":"417","DOI":"10.4049\/jimmunol.1101980","article-title":"Eosinophils preserve parasitic nematode larvae by regulating local immunity","volume":"188","author":"Gebreselassie","year":"2012","journal-title":"J Immunol"},{"issue":"9","key":"10.1016\/j.dmd.2025.100126_bib26","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1124\/dmd.107.015511","article-title":"Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes","volume":"35","author":"Aitken","year":"2007","journal-title":"Drug Metab Dispos"},{"issue":"4","key":"10.1016\/j.dmd.2025.100126_bib27","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3109\/00498254.2010.545452","article-title":"Pharmacokinetics and metabolism of BIBF 1120 after oral dosing to healthy male volunteers","volume":"41","author":"Stopfer","year":"2011","journal-title":"Xenobiotica"},{"issue":"6","key":"10.1016\/j.dmd.2025.100126_bib28","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1164\/rccm.2009-040GL","article-title":"An official ATS\/ERS\/JRS\/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management","volume":"183","author":"Raghu","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.dmd.2025.100126_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.113039","article-title":"Anti-angiogenic effect of Shikonin in rheumatoid arthritis by downregulating PI3K\/AKT and MAPKs signaling pathways","volume":"260","author":"Liu","year":"2020","journal-title":"J Ethnopharmacol"},{"key":"10.1016\/j.dmd.2025.100126_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2021.114791","article-title":"Anti-proliferation and anti-inflammation effects of corilagin in rheumatoid arthritis by downregulating NF-\u03baB and MAPK signaling pathways","volume":"284","author":"Shen","year":"2022","journal-title":"J Ethnopharmacol"},{"key":"10.1016\/j.dmd.2025.100126_bib31","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.cellsig.2016.12.003","article-title":"Attenuated JNK signaling in multidrug-resistant leukemic cells. Dual role of MAPK in cell survival","volume":"30","author":"Cerezo","year":"2017","journal-title":"Cell Signal"},{"issue":"13","key":"10.1016\/j.dmd.2025.100126_bib32","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and management of rheumatoid arthritis: a review","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA"},{"issue":"3","key":"10.1016\/j.dmd.2025.100126_bib33","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.ccm.2019.05.003","article-title":"Thoracic manifestations of rheumatoid arthritis","volume":"40","author":"Esposito","year":"2019","journal-title":"Clin Chest Med"},{"issue":"6","key":"10.1016\/j.dmd.2025.100126_bib34","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1002\/art.27405","article-title":"Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study","volume":"62","author":"Bongartz","year":"2010","journal-title":"Arthritis Rheum"},{"issue":"4","key":"10.1016\/j.dmd.2025.100126_bib35","doi-asserted-by":"crossref","first-page":"00345","DOI":"10.1183\/23120541.00345-2021","article-title":"Suppression of epithelial abnormalities by nintedanib in induced-rheumatoid arthritis-associated interstitial lung disease mouse model","volume":"7","author":"Miura","year":"2021","journal-title":"ERJ Open Res"},{"issue":"3","key":"10.1016\/j.dmd.2025.100126_bib36","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/jcph.1025","article-title":"Pharmacokinetics of nintedanib in subjects with hepatic impairment","volume":"58","author":"Marzin","year":"2018","journal-title":"J Clin Pharmacol"},{"issue":"9","key":"10.1016\/j.dmd.2025.100126_bib37","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1007\/s40262-019-00766-0","article-title":"Clinical pharmacokinetics and pharmacodynamics of nintedanib","volume":"58","author":"Wind","year":"2019","journal-title":"Clin Pharmacokinet"},{"key":"10.1016\/j.dmd.2025.100126_bib38","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.bcp.2017.06.118","article-title":"Differential changes in the pharmacokinetics of statins in collagen-induced arthritis rats","volume":"142","author":"Lin","year":"2017","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.dmd.2025.100126_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2021.114413","article-title":"Pharmacokinetics of metformin in collagen-induced arthritis rats","volume":"185","author":"Chen","year":"2021","journal-title":"Biochem Pharmacol"},{"issue":"10","key":"10.1016\/j.dmd.2025.100126_bib40","article-title":"Relationship between serum interleukin-6 levels, systemic immune-inflammation index, and other biomarkers across different rheumatoid arthritis severity levels","volume":"16","author":"Zeb","year":"2024","journal-title":"Cureus"},{"issue":"2","key":"10.1016\/j.dmd.2025.100126_bib41","doi-asserted-by":"crossref","first-page":"76","DOI":"10.5152\/eurjrheum.2018.18114","article-title":"Serum hepcidin level and rheumatoid arthritis disease activity","volume":"6","author":"Sahebari","year":"2018","journal-title":"Eur J Rheumatol"},{"issue":"15","key":"10.1016\/j.dmd.2025.100126_bib42","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.2174\/1389201024666230417091625","article-title":"Simultaneously inhibiting P-gp efflux and drug recrystallization enhanced the oral bioavailability of nintedanib","volume":"24","author":"Wang","year":"2023","journal-title":"Curr Pharm Biotechnol"},{"key":"10.1016\/j.dmd.2025.100126_bib43","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.carbpol.2018.09.080","article-title":"Nintedanib-cyclodextrin complex to improve bio-activity and intestinal permeability","volume":"204","author":"Vaidya","year":"2019","journal-title":"Carbohydr Polym"},{"key":"10.1016\/j.dmd.2025.100126_bib44","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.3389\/fimmu.2020.01300","article-title":"Sonic hedgehog regulates proliferation, migration and invasion of synoviocytes in rheumatoid arthritis via JNK signaling","volume":"11","author":"Zhu","year":"2020","journal-title":"Front Immunol"},{"issue":"3","key":"10.1016\/j.dmd.2025.100126_bib45","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1093\/rheumatology\/kead359","article-title":"Leukocyte Ig-like receptor A3 facilitates inflammation, migration and invasion of synovial tissue-derived fibroblasts via ERK\/JNK activation","volume":"63","author":"Liu","year":"2024","journal-title":"Rheumatology (Oxford)"},{"issue":"15","key":"10.1016\/j.dmd.2025.100126_bib46","first-page":"4527","article-title":"Transcription factor c-Jun activation represses mdr-1 gene expression","volume":"63","author":"Miao","year":"2003","journal-title":"Cancer Res"}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955625091354?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955625091354?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:26:32Z","timestamp":1773926792000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955625091354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":44,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["S0090955625091354"],"URL":"https:\/\/doi.org\/10.1016\/j.dmd.2025.100126","relation":{},"ISSN":["0090-9556"],"issn-type":[{"value":"0090-9556","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pharmacokinetic changes of nintedanib in collagen-induced arthritic rats are related to reduction of intestinal P-glycoprotein expression","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.dmd.2025.100126","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics.","name":"copyright","label":"Copyright"}],"article-number":"100126"}}