title: Capsaicin pretreatment increased the bioavailability of cyclosporin in rats: involvement of P-glycoprotein and CYP 3A inhibition.
abstract: Capsaicin (CAP), the main ingredient responsible for the hot pungent taste of chilli peppers. This study investigated the effect of CAP on the pharmacokinetics of Cyclosporin A (CyA) in rats and the mechanism of this food-drug interaction. The results indicated that after 7 days of low or middle dose of CAP (0.3 or 1.0 mg/kg), the blood concentration of CyA was not significantly changed compared with that of vehicle-treated rats, whereas the blood concentration of CyA in high dose group (3.0 mg/kg) was significantly increased. The total clearance (CL/F) of CyA was decreased, and the bioavailability was significantly increased to about 1.44-fold of that in vehicle-treated rats after 7 days of high dose CAP treatment. At this time, the P-gp and CYP3A1/2 in the liver and intestine were decreased at both the mRNA and protein levels. These results demonstrated that chronic ingestion of high doses of CAP will increase the bioavailability of CyA to a significant extent in rats and the food-drug interaction between CAP and CyA appears to be due to modulation of P-gp and CYP3A gene expression by CAP, with differential dose-dependence.
authors.affiliation: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Xue-jia
authors.initials: XJ
authors.lastname: Zhai
authors.forename: Fang
authors.initials: F
authors.lastname: Shi
authors.forename: Fen
authors.initials: F
authors.lastname: Chen
authors.forename: Yong-ning
authors.initials: YN
authors.lastname: Lu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D002211:Capsaicin / Q000494:pharmacology*; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D018565:Food-Drug Interactions; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D017207:Rats, Sprague-Dawley; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002211:Capsaicin; D016572:Cyclosporine; D051544:Cytochrome P-450 CYP3A; D003907:Dexamethasone; D007654:Ketoconazole; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C095122:multidrug resistance protein 3; C465260:Cyp3a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat
keywords: CYP3A; Capsaicin; Cyclosporin; Food–drug interactions; P-glycoprotein