Effect of quercetin on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in healthy subjects.
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.
Kim
Kyoung-Ah
KA
Department of Pharmacology, Gil Medical Center, Gachon Medical School, 1198 Kuwoldong, Namdong-gu, Incheon 405-760, Korea.
Park
Pil-Whan
PW
Kim
Hyung-Kee
HK
Ha
Jong-Myung
JM
Park
Ji-Young
JY
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*
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