DISPOSITION OF CLOZAPINE AND DESMETHYLCLOZAPINE IN SCHIZOPHRENIC-PATIENTS

The disposition of the atypical clozapine and its desmethyl metabolite were evaluated in fourteen male chronic patients. A single 100 mg dos e of clozapine was administered and blood sampling performed over the following 72 hours. The mean (SD) oral clearance and half-life of cloz apine were 55.4 (29.7) L/hr and 13.7 (9.9) hours, respectively. The me an (SD) AUC for clozapine and desmethylclozapine was 2389.9 (1406) and 751.1 (622.9) ng.hr/mL, respectively. The elimination of the metaboli te is rate limited by its formation from cloza-pine. A wide interpatie nt variability in clozapine and desmethylclozapine pharmacokinetics wa s observed.