Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone.

Author(s): Jalava KM, Olkkola KT, Neuvonen PJ

Affiliation(s): Department of Clinical Pharmacology, University of Helsinki, Finland.

Publication date & source: 1996, Eur J Clin Pharmacol., 51(3-4):331-4.

Publication type: Clinical Trial; Randomized Controlled Trial

OBJECTIVE: We studied the possible interaction between itraconazole, a potent inhibitor of CYP3A, and zopiclone, a short-acting hypnotic. METHODS: A double-blind, randomized, two-phase crossover design was used. Ten healthy young subjects received daily either 200 mg itraconazole or placebo for 4 days. On day 4 they ingested a single 7.5-mg oral dose of zopiclone. Plasma concentrations of zopiclone and itraconazole were determined and pharmacodynamic responses were measured up to 17 h. RESULTS: Itraconazole significantly increased the Cmax of zopiclone from 49 to 63 ng.ml-1. The t 1/2 of zopiclone was prolonged from 5.0 to 7.0 h. The AUC(0-inifinity) of zopiclone was increased from 415 to 719 ng.ml-1 h by itraconazole. No statistically significant differences were observed in the pharmacodynamic responses between the groups. CONCLUSIONS: Itraconazole has a statistically significant pharmacokinetic interaction with zopiclone but this is only of limited clinical importance, at least in young adults.