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

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dc.contributor.authorTurkanovic, J.
dc.contributor.authorNgo, S.
dc.contributor.authorMilne, R.
dc.date.issued2009
dc.description.abstractObjectives: 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 μg/ml), either alone or following addition of ciclosporin (0.5 μg/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.
dc.description.statementofresponsibilityJasmina Turkanovic, Suong N.T. Ngo and Robert W. Milne
dc.identifier.citationJournal of Pharmacy and Pharmacology, 2009; 61(8):1037-1042
dc.identifier.doi10.1211/jpp.61.08.0007
dc.identifier.issn0022-3573
dc.identifier.issn2042-7158
dc.identifier.orcidNgo, S. [0000-0002-9050-6894]
dc.identifier.urihttp://hdl.handle.net/2440/63752
dc.language.isoen
dc.publisherRoyal Pharmaceutical Society Great Britain
dc.rights© 2009 The Authors
dc.source.urihttps://doi.org/10.1211/jpp.61.08.0007
dc.subjectfexofenadine
dc.subjecthepatic transport
dc.subjectinduction
dc.subjectorganic anion transporting polypeptide
dc.subjectP-glycoprotein
dc.subjectSt John's wort
dc.titleEffect of St John's wort on the disposition of fexofenadine in the isolated perfused rat liver
dc.typeJournal article
pubs.publication-statusPublished

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