Effect of St John's wort on the disposition of fexofenadine in the isolated perfused rat liver

J TURKANOVIC, Suong Ngo, R MILNE

    Research output: Contribution to journalArticle

    Abstract

    Objectives: This study examined the effects of St John's wort (Hypericum perforatum) on the disposition of fexofenadine, a substrate of P-glycoprotein/organic anion transporting polypeptide, in the isolated perfused rat liver. Methods: Male Sprague-Dawley rats were given St John's wort, 1000 mg/kg, by intragastric gavage once daily for 14 days. On day 15, livers were isolated surgically and perfused in a recirculating system with fexofenadine (2 ?g/ml), either alone or following addition of ciclosporin (0.5 ?g/ml) 5 min before the addition of fexofenadine. Perfusate samples and bile were collected for 60 min. Fexofenadine in perfusate, bile and the homogenised livers was measured by HPLC. Key findings: Administration of St John's wort significantly increased biliary clearance with respect to perfusate and biliary clearance with respect to the concentration in the liver, by 74% and 71%, respectively. This was reversed by ciclosporin. Conclusions: St John's wort enhanced the elimination of fexofenadine into the bile. This could be because it increases the activity of P-glycoprotein on the canalicular membrane of hepatocytes. � 2009 The Authors.
    Original languageEnglish
    Pages (from-to)1037-1042
    Number of pages6
    JournalJournal of Pharmacy and Pharmacology
    Volume61
    Issue number8
    Publication statusPublished - 2009

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