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Effect of High‐Dose Aspirin on CYP2E1 Activity in Healthy Subjects Measured Using Chlorzoxazone as a Probe
Author(s) -
Park JiYoung,
Kim KyoungAh,
Park PilWhan,
Ha JongMyung
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005282635
Subject(s) - chlorzoxazone , aspirin , placebo , pharmacology , crossover study , pharmacokinetics , medicine , metabolite , confidence interval , chemistry , anesthesia , cyp2e1 , metabolism , alternative medicine , cytochrome p450 , pathology
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.