{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:42:11Z","timestamp":1790037731821,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>Using positron emission tomography imaging, we determined the hepatic concentrations and hepatobiliary transport of [<jats:sup>11<\/jats:sup>C]rosuvastatin (RSV; i.v. injection) in the absence (<jats:italic>n<\/jats:italic>\u00a0=\u00a06) and presence (<jats:italic>n<\/jats:italic>\u00a0=\u00a04 of 6) of cyclosporin A (CsA; i.v. infusion) following a therapeutic dose of unlabeled RSV (5\u00a0mg, p.o.) in healthy human volunteers. The sinusoidal uptake, sinusoidal efflux, and biliary efflux clearance (CL; mL\/minute) of [<jats:sup>11<\/jats:sup>C]RSV, estimated through compartment modeling were 1,205.6\u00a0\u00b1\u00a0384.8, 16.2\u00a0\u00b1\u00a011.2, and 5.1\u00a0\u00b1\u00a01.8, respectively (<jats:italic>n<\/jats:italic>\u00a0=\u00a06). CsA (blood concentration: 2.77\u00a0\u00b1\u00a00.24\u00a0\u03bcM), an organic\u2010anion\u2010transporting polypeptide, Na<jats:sup>+<\/jats:sup>\u2010taurocholate cotransporting polypeptide, and breast cancer resistance protein inhibitor increased [<jats:sup>11<\/jats:sup>C]RSV systemic blood exposure (45%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), reduced its biliary efflux CL (52%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and hepatic uptake (25%; <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05) but did not affect its distribution into the kidneys. CsA increased plasma concentrations of coproporphyrin I and <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> and total bilirubin by 297\u00a0\u00b1\u00a069%, 384\u00a0\u00b1\u00a0102%, and 81\u00a0\u00b1\u00a039%, respectively (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). These data can be used in the future to verify predictions of hepatic concentrations and hepatobiliary transport of RSV.<\/jats:p>","DOI":"10.1002\/cpt.1506","type":"journal-article","created":{"date-parts":[[2019,5,18]],"date-time":"2019-05-18T14:39:39Z","timestamp":1558190379000},"page":"1056-1066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Positron Emission Tomography Imaging of [<sup>11<\/sup>C]Rosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporin A"],"prefix":"10.1111","volume":"106","author":[{"given":"Sarah","family":"Billington","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics University of Washington  Seattle Washington USA"},{"name":"Drug Metabolism and Pharmacokinetics Vertex Pharmaceuticals (Europe) Ltd.  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