title: Effect of quercetin on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in healthy subjects.
abstract: Previous in vitro studies have demonstrated that quercetin inhibits CYP2C8, but there are no available data to indicate that quercetin inhibits CYP2C8 in vivo. The effect of long-term use of quercetin on the pharmacokinetics of rosiglitazone was evaluated. After administration of quercetin or matched placebo for 3 weeks in a crossover manner, rosiglitazone 4 mg was administered, and the pharmacokinetics of rosiglitazone and N-desmethylrosiglitazone were determined. For AUCinfinity, AUClast, and Cmax, the geometric mean ratios (90% confidence interval) for (quercetin + rosiglitazone/placebo + rosiglitazone) were 0.98 (0.92, 1.05), 0.99 (0.92, 1.05), and 1.01 (0.88, 1.14), respectively. Metabolic conversion based on the AUC ratio of N-desmethylrosiglitazone/rosiglitazone in the quercetin phase (0.49 +/- 0.17) was similar to that of the placebo phase (0.47 +/- 0.14) (P = .574). Even though the acute interaction that would occur during the first few days of concurrent administration of quercetin cannot be excluded, these results indicate that long-term use of quercetin does not inhibit CYP2C8 activity, and the usage has little possibility of interacting with drugs that are metabolized by CYP2C8, including rosiglitazone.
authors: Department of Pharmacology, Gil Medical Center, Gachon Medical School, 1198 Kuwoldong, Namdong-gu, Incheon 405-760, Korea.
authors: Kyoung-Ah
authors: KA
authors: Kim
authors: Pil-Whan
authors: PW
authors: Park
authors: Hyung-Kee
authors: HK
authors: Kim
authors: Jong-Myung
authors: JM
authors: Ha
authors: Ji-Young
authors: JY
authors: Park
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018592:Cross-Over Studies; D065727:Cytochrome P-450 CYP2C8; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D007004:Hypoglycemic Agents; C480687:N-desmethylrosiglitazone; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011794:Quercetin; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8