Effect of high-dose aspirin on CYP2E1 activity in healthy subjects measured using chlorzoxazone as a probe.
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.
Park
Ji-Young
JY
Department of Pharmacology, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, Korea.
Kim
Kyoung-Ah
KA
Park
Pil-Whan
PW
Ha
Jong-Myung
JM
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002753:Chlorzoxazone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D004334:Drug Administration Schedule; D006801:Humans; D007723:Korea; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male
D000894:Anti-Inflammatory Agents, Non-Steroidal; C039289:6-hydroxychlorzoxazone; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone; D001241:Aspirin