Disposition of Clozapine and Desmethylclozapine in Schizophrenic Patients

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Abstract
The disposition of the atypical clozapine and its desmethyl metabolite were evaluated in fourteen male chronic patients. A single 100 mg dose of clozapine was administered and blood sampling performed over the following 72 hours. The mean (SD) oral clearance and half‐life of clozapine were 55.4 (29.7) L/hr and 13.7 (9.9) hours, respectively. The mean (SD) AUC for clozapine and desmethylclozapine was 2389.9 (1406) and 751.1 (622.9) ng ·; hr/mL, respectively. The elimination of the metabolite is rate limited by its formation from cloza‐pine. A wide interpatient variability in clozapine and desmethylclozapine pharmacokinetics was observed.