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Current Drug Safety

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ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

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Research Article

Influence of Quercetin Pretreatment on Pharmacokinetics of Warfarin in Rats

Author(s): Ejaz Ahmad, Muhammad Jahangir*, Muhammad Akhter Ismail, Hafsa Afzal, Shehar Bano, Rahat Shamim and Nadeem Irfan Bukhari

Volume 18, Issue 4, 2023

Published on: 03 November, 2022

Page: [547 - 554] Pages: 8

DOI: 10.2174/1574886317666221014101201

Price: $65

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 15th 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 Cmax was increased by 30.43%, AUC0-∞ by 62.94%, and t1/2 by 10.54%, while Cl decreased by 41.35%, relative to control. In co-administered animals, WAR’s Cmax increased by 10.98%, AUC0-∞ by 20.20%, and t1/2 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.

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