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 journalArticleResearchpeer-review

    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

    Keywords

    • cyclosporin A
    • fexofenadine
    • Hypericum perforatum extract
    • cyclosporin
    • drug derivative
    • glycoprotein P
    • histamine H1 receptor antagonist
    • plant extract
    • terfenadine
    • animal experiment
    • animal tissue
    • area under the curve
    • article
    • biliary excretion
    • controlled study
    • drug absorption
    • drug bile level
    • drug clearance
    • drug disposition
    • drug potentiation
    • high performance liquid chromatography
    • isolated liver
    • liver homogenate
    • liver perfusion
    • male
    • nonhuman
    • rat
    • animal
    • chemistry
    • drug effect
    • drug interaction
    • Hypericum
    • liver
    • liver cell
    • metabolism
    • Sprague Dawley rat
    • Animals
    • Chromatography, High Pressure Liquid
    • Cyclosporine
    • Drug Interactions
    • Hepatocytes
    • Histamine H1 Antagonists, Non-Sedating
    • Liver
    • Male
    • P-Glycoprotein
    • Plant Extracts
    • Rats
    • Rats, Sprague-Dawley
    • Terfenadine

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