{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T23:01:17Z","timestamp":1763766077662,"version":"3.40.4"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,3,4]],"date-time":"2014-03-04T00:00:00Z","timestamp":1393891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"crossref","award":["2012R1A1A1005896"],"award-info":[{"award-number":["2012R1A1A1005896"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002648","name":"The Catholic University of Korea","doi-asserted-by":"crossref","award":["M-2012-B0002-00031"],"award-info":[{"award-number":["M-2012-B0002-00031"]}],"id":[{"id":"10.13039\/501100002648","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Under hyperlipidemic conditions, there are likely to be alterations in the pharmacokinetics of CYP2C11 substrates following decreased expression of CYP2C11, which is homologous to human CYP2C9. The pharmacokinetics of tolbutamide (TB) and its metabolite 4\u2010hydroxy tolbutamide (4\u2010OHTB) were evaluated as a CYP2C11 probe after intravenous and oral administration of 10 mg\/kg tolbutamide to poloxamer 407\u2010induced hyperlipidemic rats (HL rats). Changes in the expression and metabolic activity of hepatic CYP2C11 and the plasma protein binding of tolbutamide in HL rats were also evaluated. The total area under the plasma concentration\u2013time curve (<jats:italic>AUC<\/jats:italic>) of tolbutamide in HL rats after intravenous administration was comparable to that in controls due to their comparable non\u2010renal clearance (<jats:italic>CL<\/jats:italic><jats:sub>NR<\/jats:sub>). The free fractions of tolbutamide in plasma were comparable between the control and HL rats. The 4\u2010hydroxylated metabolite formation ratio (<jats:italic>AUC<\/jats:italic><jats:sub>4\u2010OHTB<\/jats:sub>\/<jats:italic>AUC<\/jats:italic><jats:sub>TB<\/jats:sub>) in HL rats was significantly smaller than that in the control rats as a result of the reduced expression of hepatic CYP2C11 (by 15.0%) and decreased hepatic<jats:italic>CL<\/jats:italic><jats:sub>int<\/jats:sub>(by 28.8%) for metabolism of tolbutamide to 4\u2010OHTB via CYP2C11. Similar pharmacokinetic changes were observed in HL rats after oral administration of tolbutamide. These findings have potential therapeutic implications, assuming that the HL rat model qualitatively reflects similar changes in patients with hyperlipidemia. Since other sulfonylureas in clinical use are substrates of CYP2C9, their hepatic<jats:italic>CL<\/jats:italic><jats:sub>int<\/jats:sub>changes have the potential to cause clinically relevant pharmacokinetic changes in a hyperlipidemic state. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.1893","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T12:12:11Z","timestamp":1392639131000},"page":"264-274","source":"Crossref","is-referenced-by-count":13,"title":["Pharmacokinetics of tolbutamide and its metabolite 4\u2010hydroxy tolbutamide in poloxamer 407\u2010induced hyperlipidemic rats"],"prefix":"10.1002","volume":"35","author":[{"given":"Mi Ran","family":"Choi","sequence":"first","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences The Catholic University of Korea Bucheon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi Hye","family":"Kwon","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences The Catholic University of Korea Bucheon South 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