title: Food-drug interactions: effect of capsaicin on the pharmacokinetics of simvastatin and its active metabolite in rats.
abstract: Capsaicin (trans-8-methy-N-vanilly-6-nonenamide, CAP), the main ingredient responsible for the hot pungent taste of chilli peppers. However, little is known about the metabolic interactions between CAP and clinically used drugs. This study attempted to investigate the effect of CAP on the pharmacokinetics of simvastatin (SV), a cytochrome P450 (CYP) 3A substrate and an important cholesterol-lowering agent. CAP (3, 8 or 25 mg/kg), ketoconazole, dexamethasone or 5% CMC-Na was given to rats for seven consecutive days and on the seventh day SV (80 mg/kg) was administered orally. The results showed that when a single dose of SV was administered to rats fed with CAP over one week, AUC(0→∞), C(max) of SV and its acid metabolite was significantly decreased in comparison to the control treatment. Pretreatment of rats with CAP resulted in an decrease in the AUC(0-∞) of SV of about 67.06% (CAP 3 mg/kg, P<0.05), 73.21% (CAP 8 mg/kg, P<0.01) and 77.49% (CAP 25 mg/kg, P<0.01) compared with the control group. The results demonstrate that chronic ingestion of high doses of CAP will decrease the bioavailability of SV to a significant extent in rats.
authors.affiliation: Department of Pharmacy, Union Hospital, 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: Jian-guo
authors.initials: JG
authors.lastname: Chen
authors.forename: Jin-mei
authors.initials: JM
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Shi
authors.forename: Yong-ning
authors.initials: YN
authors.lastname: Lu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002211:Capsaicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002212:Capsicum / Q000737:chemistry; D002853:Chromatography, Liquid; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D018565:Food-Drug Interactions; D007654:Ketoconazole / Q000008:administration & dosage; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000924:Anticholesteremic Agents; D003907:Dexamethasone; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A; D007654:Ketoconazole; D002211:Capsaicin