title: Pharmacokinetic interaction between zolpidem and carbamazepine in healthy volunteers.
abstract: 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.
authors.affiliation: University of Medicine and Pharmacy, Iuliu Haţieganu, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, Romania. vlaselaur@yahoo.com
authors.forename: Laurian
authors.initials: L
authors.lastname: Vlase
authors.forename: Adina
authors.initials: A
authors.lastname: Popa
authors.forename: Maria
authors.initials: M
authors.lastname: Neag
authors.forename: Dana
authors.initials: D
authors.lastname: Muntean
authors.forename: Ioan
authors.initials: I
authors.lastname: Bâldea
authors.forename: Sorin E
authors.initials: SE
authors.lastname: Leucuţa
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D001682:Biological Availability; D002220:Carbamazepine / Q000494:pharmacology*; D018592:Cross-Over Studies; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D058785:GABA-A Receptor Agonists / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult; D000077334:Zolpidem
chemical_list: D000927:Anticonvulsants; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D011725:Pyridines; D002220:Carbamazepine; D000077334:Zolpidem; D003577:Cytochrome P-450 Enzyme System