Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone.
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.
Jalava
K M
KM
Department of Clinical Pharmacology, University of Helsinki, Finland.
Olkkola
K T
KT
Neuvonen
P J
PJ
D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds; D018592:Cross-Over Studies; D065607:Cytochrome P-450 Enzyme Inhibitors; D004311:Double-Blind Method; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D017964:Itraconazole / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics*
D000935:Antifungal Agents; D053961:Azabicyclo Compounds; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; D017964:Itraconazole