Turkanovic, J.Ngo, S.Milne, R.2011-05-192011-05-192009Journal of Pharmacy and Pharmacology, 2009; 61(8):1037-10420022-35732042-7158http://hdl.handle.net/2440/63752Objectives: 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.en© 2009 The Authorsfexofenadinehepatic transportinductionorganic anion transporting polypeptideP-glycoproteinSt John's wortJournal article002010595210.1211/jpp.61.08.00070002695012000072-s2.0-7024913404930934Ngo, S. [0000-0002-9050-6894]