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Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers

The purpose of present study was to evaluate the effect of quercetin on pharmacokinetics of diclofenac sodium (DIC) in healthy volunteers. The open‐label, 2 period, sequential study was conducted in 12 healthy volunteers. DIC 100 mg was administered during control and after quercetin phases. Quercetin 500 mg was administered twice daily for 10 days during quercetin phase. Treatment with quercetin significantly enhanced maximum plasma concentration (Cmax), area under the curve (AUC0‐∞), and half life, while significantly decreased elimination rate constant (kel) and apparent oral clearance (CL/F) of DIC compared with control. On the other hand, Cmax and AUC0‐∞ of 4‐hydroxydiclofenac (4‐OHDIC) were decreased after quercetin treatment. In addition, geometric mean ratios and 90% confidence intervals for Cmax and AUC0‐∞ of DIC and 4‐OHDIC were both out of the no‐effect limits of 0.80–1.25, which indicates a significant pharmacokinetic interaction between quercetin and DIC. Furthermore, quercetin treatment significantly decreased metabolic ratios of Cmax and AUC0‐∞ suggesting that reduced formation of DIC to 4‐OHDIC. The results suggest that quercetin might have inhibited CYP2C9‐mediated metabolism of DIC. Accordingly, caution should be taken when quercetin is used in combination with therapeutic drugs metabolized by CYP2C9, and dose adjustment of CYP2C9 substrates may be necessary.