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Objective. To clarify the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of etizolam. Methods. The effects of itraconazole, a potent and specific inhibitor of CYP3A4, on the single oral dose pharmacokinetics and pharmacodynamics of etizolam were examined. Twelve healthy male volunteers received itraconazole (200 mg/day) or placebo for 7 days in a double-blind randomized crossover manner, and on the 6th day they received a single oral 1-mg dose of etizolam. Blood samplings and evaluation of psychomotor function using the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 24 h after etizolam dosing. Plasma concentration of etizolam was measured by means of high-performance liquid chromatography. Results. Itraconazole treatment significantly increased the total area under the plasma concentration–time curve (AUC; 213±106 ng⁃h/ml versus 326±166 ng⁃h/ml, P<0.001) and the elimination half-life (12.0±5.4 h versus 17.3±7.4 h, P<0.01) of etizolam. The 90% confidence interval of the itraconazole/placebo ratio of the total AUC was 1.38–1.68, indicating a significant effect of itraconazole. No significant change was induced by itraconazole in the two pharmacodynamic parameters. Conclusion. The present study suggests that itraconazole inhibits the metabolism of etizolam, providing evidence that CYP3A4 is at least partly involved in etizolam metabolism. [ABSTRACT FROM AUTHOR]