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


CONCLUSIONS
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.
Raaska
K
K
Kellokoski Hospital, Finland.
Neuvonen
P J
PJ
D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics*; D003024:Clozapine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy
D000935:Antifungal Agents; D014150:Antipsychotic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; C058272:norclozapine; D017964:Itraconazole; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D003024:Clozapine