title: Capsaicin pretreatment enhanced the bioavailability of fexofenadine in rats by P-glycoprotein modulation: in vitro, in situ and in vivo evaluation.
abstract: OBJECTIVE
  Capsaicin is the main pungent principle present in chili peppers has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro, which may have the potential to modulate bioavailability of P-gp substrates. Therefore, purpose of this study was to evaluate the effect of capsaicin on intestinal absorption and bioavailability of fexofenadine, a P-gp substrate in rats.
  
  
  METHODS
  The mechanistic evaluation was determined by non-everted sac and intestinal perfusion studies to explore the intestinal absorption of fexofenadine. These results were confirmed by an in vivo pharmacokinetic study of oral administered fexofenadine in rats.
  
  
  RESULTS
  The intestinal transport and apparent permeability (Papp) of fexofenadine were increased significantly by 2.8 and 2.6 fold, respectively, in ileum of capsaicin treated rats when compared to control group. Similarly, absorption rate constant (Ka), fraction absorbed (Fab) and effective permeability (Peff) of fexofenadine were increased significantly by 2.8, 2.9 and 3.4 fold, respectively, in ileum of rats pretreated with capsaicin when compared to control group. In addition, maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were increased significantly by 2.3 and 2.4 fold, respectively, in rats pretreated with capsaicin as compared to control group. Furthermore, obtained results in rats pretreated with capsaicin were comparable to verapamil (positive control) treated rats.
  
  
  CONCLUSIONS
  Capsaicin pretreatment significantly enhanced the intestinal absorption and bioavailability of fexofenadine in rats likely by inhibition of P-gp mediated cellular efflux, suggesting that the combined use of capsaicin with P-gp substrates may require close monitoring for potential drug interactions.
authors.affiliation: a Drug Metabolism and Pharmacokinetics Division , University College of Pharmaceutical Sciences, Kakatiya University , Warangal , India.
authors.forename: Satish Kumar
authors.initials: SK
authors.lastname: Bedada
authors.affiliation: b Department of Pharmaceutical Chemistry , Nethaji Institute of Pharmaceutical Sciences, Kakatiya University , Warangal , India.
authors.forename: Ramgopal
authors.initials: R
authors.lastname: Appani
authors.affiliation: a Drug Metabolism and Pharmacokinetics Division , University College of Pharmaceutical Sciences, Kakatiya University , Warangal , India.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Boga
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002211:Capsaicin / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D010477:Perfusion; D010539:Permeability / Q000187:drug effects; D011433:Propranolol / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000319:Adrenergic beta-Antagonists; D006634:Histamine H1 Antagonists; D016593:Terfenadine; D011433:Propranolol; C093230:fexofenadine; D002211:Capsaicin
keywords: Capsaicin; P-glycoprotein; bioavailability; fexofenadine; pharmacokinetics