Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone

Abstract

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 C_max 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–∞) 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.

Conclusion:

Itraconazole has a statistically significant pharmacokinetic interaction with zopiclone but this is only of limited clinical importance, at least in young adults.