Induction of the metabolism of etizolam by carbamazepine in humans

Abstract

Objective: To examine the effect of carbamazepine on the single oral dose pharmacokinetics of etizolam.

Methods: Eleven healthy male volunteers received carbamazepine 200 mg/day or placebo for 6 days in a double-blind, randomized, crossover manner, and on the sixth day they received a single oral 1-mg dose of etizolam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 24 h after etizolam dosing. Plasma concentration of etizolam was measured using high-performance liquid chromatography.

Results: Carbamazepine treatment significantly decreased the peak plasma concentration (17.5+/-4.1 ng/ml versus 13.9+/-4.1 ng/ml; P<0.05), total area under the plasma concentration-time curve (194.8+/-88.9 ng h/ml versus 105.9+/-33.0 ng h/ml; P<0.001), and elimination half-life (11.1+/-4.6 h versus 6.8+/-2.8 h; P<0.01) of etizolam. No significant change was induced by carbamazepine in the two pharmacodynamic parameters.

Conclusions: The present study suggests that carbamazepine induces the metabolism of etizolam.