No effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of estazolam.

To examine the involvement of cytochrome P450 3A4 in the metabolism of estazolam, the effect of itraconazole, a potent inhibitor of this enzyme, on the single oral dose pharmacokinetics and pharmacodynamics of estazolam was studied in a double-blind randomized crossover manner. Ten healthy male volunteers received itraconazole 100 mg/day or placebo orally for 7 days, and on the 4th day they received a single oral 4-mg dose of estazolam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test, Visual Analog Scale, and Stanford Sleepiness Scale were conducted up to 72 hours after estazolam dosing. There was no significant difference between the placebo and itraconazole phases for the peak plasma concentration, apparent oral clearance, and elimination half-life. Similarly, none of the psychomotor function parameters was significantly different between the two phases. The current study showed no significant effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of estazolam, suggesting that cytochrome P450 3A4 is not involved in the metabolism of estazolam to a major extent.