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Tian XB , Swift B , Zamek-Gliszczynski MJ , Belinsky MG , Kruh GD , Brouwer KLR
Impact of basolateral multidrug resistance-associated protein (Mrp) 3 and Mrp4 on the hepatobiliary disposition of fexofenadine in perfused mouse livers
Drug Metabolism and Disposition. 2008 May;36(5) :911-915
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Abstract
The disposition of fexofenadine, a commonly used antihistamine drug, is governed primarily by active transport. Biliary excretion of the parent compound is the major route of systemic clearance. Previous studies demonstrated that fexofenadine hepatic uptake is mediated by organic anion transporting polypeptides. Recently, we showed that in mice fexofenadine is excreted into bile primarily by multidrug resistance-associated protein (Mrp) 2 (Abcc2). In the present study, the roles of Mrp3 (Abcc3) and Mrp4 (Abcc4) in the hepatobiliary disposition of fexofenadine were examined in knockout mice using in situ liver perfusion. Compared with that in wildtype mice, basolateral excretion of fexofenadine was impaired, resulting in a similar to 50% decrease in perfusate recovery in Abcc3(-/-) mice; in contrast, fexofenadine hepatobiliary disposition was unaltered in Abcc4(-/-) mice. As expected, in Abcc2(-/-) mice, fexofenadine was redirected from the canalicular to the basolateral m!
Notes
Tian, Xianbin Swift, Brandon Zamek-Gliszczynski, Maciej J. Belinsky, Martin G. Kruh, Gary D. Brouwer, Kim L. R. AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS