Serum concentrations of clozapine and N-desmethylclozapine are unaffected by the potent CYP3A4 inhibitor itraconazole

Abstract

Objective: We studied a possible pharmacokinetic interaction between clozapine and itraconazole, a potent CYP3A4 inhibitor.

Methods: A double-blind randomized study design was used. Seven schizophrenic inpatients volunteered to receive, in addition to their previous drug regimen, either 200 mg itraconazole or placebo for 7 days. For the next 7 days, itraconazole was changed to placebo and vice versa. Serum concentrations of clozapine and its main metabolite desmethylclozapine were measured on days 0, 3, 7, 10 and 14.

Results: Concomitant administration of itraconazole had no significant effect on serum concentrations of clozapine or desmethylclozapine.

Conclusion: CYP3A4 seems to be of minor importance in clozapine metabolism in humans. Itraconazole, and probably also other inhibitors of CYP3A4, can be used concomitantly with clozapine.