LACK OF MULTIPLE DOSING EFFECT OF SERTINDOLE ON THE PHARMACOKINETICS OF ALPRAZOLAM IN HEALTHY-VOLUNTEERS

The effect of sertindole (a new selective antipsychotic compound) on t he pharmacokinetic disposition of alprazolam was investigated. Fourtee n subjects who completed the study received a single 1 mg dose of alpr azolam without or with concomitant sertindole 12 mg daily. Coadministr ation of sertindole and alprazolam led to a half-hour decrease (P < 0. 05) in mean T-max value (alone: 1.2 h, in combination: 0.7 h) and a 1. 6-h increase in the mean t(1/2) value (12.5 +/- 3.2 versus 14.3 +/- 3. 4 h, P < 0.05) of alprazolam. The mean C-max (18.5 +/- 4.9 versus 18.5 +/- 4.8 ng/ml) and AUC (266 +/- 68 versus 275 +/- 57 ng . h/ml) value s of alprazolam did not change statistically significantly in the pres ence of sertindole (P > 0.05). These pharmacokinetic changes are minor and not considered to be of clinical significance. Although both sert indole and alprazolam are substrate for CYP3A4 (cytochrome P-450 3A4), the results in this study suggest that sertindole is not an inhibitor of the metabolism of alprazolam.