J Clin Pharmacol
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DRUG INTERACTIONS

Effect of Quercetin on the Pharmacokinetics of Rosiglitazone, a CYP2C8 Substrate, in Healthy Subjects

Kyoung-Ah Kim, PhD, Pil-Whan Park, MD, PhD, Hyung-Kee Kim, MD, PhD, Jong-Myung Ha, PhD and Ji-Young Park, MD, PhD

From the Departments of Pharmacology (Dr K-A. Kim, Dr J-Y. Park) and Laboratory Medicine (Dr P-W. Park), Gil Medical Center, Clinical Trial Center, Gachon Medical School, Incheon, Korea; Department of Clinical Pharmacology, Soonchunhyang University, Chonan, Korea (Dr H-K. Kim); and Department of Biotechnology and Bioscience, Silla University, Busan, Korea (Dr Ha).

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 AUC{tau}, 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.

Key Words: Quercetin • rosiglitazone • cytochrome P450 2C8 (CYP2C8) • drug interaction

Address for reprints: Ji-Young Park, MD, PhD, Department of Pharmacology, Gachon Medical School, 1198 Kuwoldong, Namdong-gu, Incheon 405-760, Korea.


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