{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:33:12Z","timestamp":1791822792319,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The organic anion transporting polypeptide (OATP) 2B1 is expressed in pharmacokinetically relevant organs such as the liver, the kidney, and the small intestine and it is known to transport a broad range of substrates including statins. In pharmacokinetic studies applying two rat models\u2014one deficient for rat Oatp2b1 and the other expressing the human transporter\u2014we investigated the disposition of atorvastatin, a known OATP2B1 substrate, and observed a reduced exposure and an increased clearance of this OATP2B1 substrate in humanized rats compared to knockout animals. Atorvastatin is predominantly cleared via the bile and due to the clearance increase, we assessed hepatic accumulation of this OATP2B1 substrate. Blood and organs were collected 1\u2009h after administration of the HMG\u2010CoA reductase inhibitor via tail vein injection. Sample analysis revealed lower drug concentrations in serum but also 40% lower hepatic atorvastatin levels in <jats:italic>SLCO2B1<\/jats:italic>\u2010humanized rats compared to knockout animals, despite the expected role of OATP2B1 in facilitating hepatocellular uptake. Expression analysis of other drug transporters involved in hepatocellular handling of atorvastatin in treatment\u2010naive rats revealed no differences in the sinusoidal uptake transporter rOatp1b2 and the canalicular efflux transporters rBcrp and rMdr1a between genotypes. However, transcript and protein analysis of rCyp3a1 in liver tissues showed approximately 3\u2010fold higher levels in <jats:italic>SLCO2B1<\/jats:italic>\u2010humanized rats compared to <jats:italic>rSlco2b1<\/jats:italic>\u2010knockout animals. The increase in rCyp3a1 levels likely reflects an enhanced metabolic rate leading to lower hepatic atorvastatin content. Our finding suggests that humanization of OATP2B1 might influence hepatic disposition of rCyp3a1 substrates.<\/jats:p>","DOI":"10.1002\/prp2.70133","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T09:00:21Z","timestamp":1750410021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Insights Into Atorvastatin Pharmacokinetics in Rats Reveal Regulation of CYP3A1 by Humanization of <i>SLCO2B1<\/i>"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2830-2126","authenticated-orcid":false,"given":"Jonny","family":"Kinzi","sequence":"first","affiliation":[{"name":"Biopharmacy, Department of Pharmaceutical Sciences University of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Hussner","sequence":"additional","affiliation":[{"name":"Biopharmacy, Department of Pharmaceutical Sciences University 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