Pharmacokinetic Interaction Between Zolpidem and Carbamazepine in Healthy Volunteers

• Published in: Journal of clinical pharmacology 2011-08, Vol.51 (8), p.1233-1236
• Main Authors: Vlase, Laurian, Popa, Adina, Neag, Maria, Muntean, Dana, Bâldea, Ioan, Leucuta, Sorin E.
• Format: Article
• Language: English
• Subjects: Adult; Anticonvulsants - pharmacology; Biological Availability; carbamazepine; Carbamazepine - pharmacology; Cross-Over Studies; Cytochrome P-450 Enzyme System - biosynthesis; drug interaction; Drug Interactions; Enzyme Induction - drug effects; GABA-A Receptor Agonists - blood; GABA-A Receptor Agonists - pharmacokinetics; Half-Life; Humans; Hypnotics and Sedatives - blood; Hypnotics and Sedatives - pharmacokinetics; Male; Metabolic Clearance Rate; pharmacokinetics; Pyridines - blood; Pyridines - pharmacokinetics; Young Adult; Zolpidem
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270010383690

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 (Cmax) were 59 ng/mL (zolpidem alone) and 35 ng/mL (zolpidem after pretreatment with carbamazepine). The tmax, times taken to reach Cmax, were 0.9 hours and 1.0 hour, respectively, and the total areas under the curve (AUC0‐∞) 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.