title: Effect of St John's wort on the disposition of fexofenadine in the isolated perfused rat liver.
abstract: OBJECTIVE
  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 microg/ml), either alone or following addition of ciclosporin (0.5 microg/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.
  
  
  RESULTS
  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.
authors.affiliation: Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Turkanovic
authors.forename: Suong N T
authors.initials: SN
authors.lastname: Ngo
authors.forename: Robert W
authors.initials: RW
authors.lastname: Milne
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000494:pharmacology; D004347:Drug Interactions; D022781:Hepatocytes / Q000187:drug effects; D039563:Histamine H1 Antagonists, Non-Sedating / Q000493:pharmacokinetics*; D020902:Hypericum / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D039563:Histamine H1 Antagonists, Non-Sedating; D010936:Plant Extracts; D016593:Terfenadine; D016572:Cyclosporine; C093230:fexofenadine