Pharmacokinetic Interaction Between Zolpidem and Carbamazepine in Healthy Volunteers

The objective of this study was to evaluate the pharmacokinetic interaction between zolpidem and carbamazepine in healthy volunteers. The study consisted of 2 periods: period 1 (reference), when each volunteer received a single dose of 5 mg zolpidem, and period 2 (test), when each volunteer received a single dose of 5 mg zolpidem and 400 mg carbamazepine. Between the 2 periods, the participants were treated for 15 days with a single daily dose of 400 mg carbamazepine. Pharmacokinetic parameters of zolpidem administered in each treatment period were calculated using noncompartmental analysis. In the 2 periods of treatments, the mean peak plasma concentrations (C max ) were 59 ng/mL (zolpidem alone) and 35 ng/mL (zolpidem after pretreatment with carbamazepine). The t max , times taken to reach C max , were 0.9 hours and 1.0 hour, respectively, and the total areas under the curve (AUC 0‐∞ ) were 234.9 ng·h/mL and 101.5 ng·h/mL, respectively. The half‐life of zolpidem was 2.3 and 1.6 hours, respectively. Carbamazepine interacts with zolpidem in healthy volunteers and lowers its bioavailability by about 57%. The experimental data demonstrate the pharmacokinetic interaction between zolpidem and carbamazepine and suggest that the observed interaction may be clinically significant, but its relevance has to be confirmed.