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Effect of High-Dose Aspirin on CYP2E1 Activity in Healthy Subjects Measured Using Chlorzoxazone as a Probe

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

The authors evaluated the effect of high-dose aspirin at a therapeutic dose, using chlorzoxazone as a probe for CYP2E1 enzyme activity. In a randomized, open-label, 2-way crossover study, 10 healthy men were treated 3 times daily for 6 days with 1 g aspirin or placebo. On day 7, 1 dose of 400 mg chlorzoxazone was administered orally. Plasma concentrations of chlorzoxazone and its metabolite, 6-hydroxychlorzoxazone, were measured. During the aspirin phase, the area under the time-concentration curve (AUC) and peak plasma concentration of chlorzoxazone were 95% (90% confidence interval [CI], 87%-103%) and 90% (90% CI, 80%-101%) of the values during the placebo phase, respectively. High-dose aspirin did not affect the oral clearance of chlorzoxazone significantly (90% CI, 98%-120%; P = .24). The AUC ratio and plasma concentration ratios of 6-hydroxychlorzoxazone/chlorzoxazone were not changed significantly by high-dose aspirin. High-dose aspirin at a therapeutic dose does not affect CYP2E1 activity in humans.

Key Words: Aspirin • chlorzoxazone, 6-hydroxychlorzoxazone • cytochrome P450 2E1 (CYP2E1) • drug interaction

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

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