{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:00Z","timestamp":1786977540944,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:p>\n                    Understanding transporter\u2010mediated drug disposition and pharmacokinetics (PK) in patients with nonalcoholic fatty liver disease (NAFLD) is critical in developing treatment options. Here, we quantified the expression levels of major drug transporters in healthy, steatosis, and nonalcoholic steatohepatitis (NASH) liver samples, via liquid\u2010chromatography tandem mass spectrometry\u2010based proteomics, and used the data to predict the PK of substrate drugs in the disease state. Expression of organic anion transporting polypeptides (OATPs) and multidrug resistance\u2010associated protein (MRP)2 is significantly lower in NASH livers; whereas MRP3 is induced while no change was observed for organic cation transporter (OCT)1. Physiologically\u2010based pharmacokinetic models verified with PK data from healthy subjects well recovered the PK in NASH subjects for morphine (involving OCT1) and its glucuronide metabolites (MRP2\/MRP3\/OATP1B),\n                    <jats:sup>99m<\/jats:sup>\n                    TC\u2010mebrofenen (OATP1B\/MRP2\/MRP3), and rosuvastatin (OATP1B\/breast cancer resistance protein). Overall, considerations to altered protein expression can enable quantitative prediction of PK changes in subjects with NAFLD.\n                  <\/jats:p>","DOI":"10.1002\/cpt.1699","type":"journal-article","created":{"date-parts":[[2019,10,20]],"date-time":"2019-10-20T10:18:10Z","timestamp":1571566690000},"page":"1128-1137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Quantitative Proteomics and Mechanistic Modeling of Transporter\u2010Mediated Disposition in Nonalcoholic Fatty Liver Disease"],"prefix":"10.1111","volume":"107","author":[{"given":"Anna","family":"Vildhede","sequence":"first","affiliation":[{"name":"Medicine Design Worldwide R&amp;D Pfizer Inc. Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Kimoto","sequence":"additional","affiliation":[{"name":"Medicine Design Worldwide R&amp;D Pfizer Inc. 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