Influence of Quercetin Pretreatment on Pharmacokinetics of Warfarin in Rats

Abstract

Background: Warfarin (WAR) is an anticoagulant with a narrow therapeutic index and is principally metabolized by CYP3A4 and CYP2C9 enzymes. The inhibitors of these enzymes may alter the systemic exposure to WAR. Quercetin (QUE), a bioflavonoid, may modify the bioavailability of drugs used concurrently by inhibiting CYP3A4, CYP2C8, CYP2C9, CYP1A2, and Pglycoprotein (P-gp).

Objective: The current study scrutinized the influence of QUE on WAR pharmacokinetics in rats.

Method: QUE was orally administered to animals for 14 consecutive days, followed by WAR as a single oral dose on the 15^th day in the pre-treatment group. The co-administration group received a single dose of QUE and WAR concomitantly. Only carboxymethylcellulose (CMC) 0.5% was administered as a vehicle to control group.

Results: In the pre-treated group, WAR's C_max was increased by 30.43%, AUC_0-∞ by 62.94%, and t_1/2 by 10.54%, while Cl decreased by 41.35%, relative to control. In co-administered animals, WAR's C_max increased by 10.98%, AUC_0-∞ by 20.20%, and t_1/2 by 8.87%, while Cl declined by 16.40%.

Conclusion: QUE alters the pharmacokinetics of WAR, warranting possibly WAR dose adjustment after confirmatory clinical investigations, specifically in patients with thrombotic disorders and a pre-treatment history of QUE or its product.

Keywords: Quercetin; bioavailability; drug; interactions; pharmacokinetic; warfarin.