EFFECT OF CARBAMAZEPINE ON THE SINGLE ORAL DOSE PHARMACOKINETICS OF ALPRAZOLAM

The effect of carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics of alprazolam was examined in a double-blind, randomized crossover study with two phases. Seven hea lthy male subjects took carbamazepine 300 mg/day or matched placebo or ally for 10 days, and on the 8th day they took a single oral 0.8 mg do se of alprazolam. Blood samples were taken and psychomotor function wa s assessed by the Digit Symbol Substitution Test, Visual Analog Scale, and UKU Side Effect Rating Scale up to 48 h after alprazolam dosing. Carbamazepine significantly (p < .01 to .001) decreased the plasma alp razolam concentrations during the elimination phase. Carbamazepine sig nificantly (p < .001) increased the apparent oral clearance (0.90 +/- 0.21 vs. 2.13 +/- 0.54 ml/min/kg) and shortened the elimination half-l ife (17.1 +/- 4.9 vs. 7.7 +/- 1.7 h), with no significant effect on th e peak plasma concentration (11.7 +/- 1.5 vs. 13.0 +/- 3.5 ng/ml). The majority of psychomotor function parameters during the carbamazepine treatment were not significantly different from those during the place bo treatment, probably because of the sedative effect of carbamazepine itself. The present study suggests that carbamazepine decreases plasm a concentration of alprazolam by inducing its metabolism. It also supp orts the previous studies, suggesting that alprazolam is metabolized p redominantly by CYP3A4. (C) 1998 American College of Neuropsychopharma cology. Published by Elsevier Science Inc.