A target-dose finding study of clozapine in patients with schizophrenia

Evidence from recent studies suggests that clozapine plasma concentrations greater than 350 ng/ml are correlated with therapeutic response. However, little is known about the clozapine dosages required to achieve these plasma concentrations. The purpose of this study was to determine if a target dose of 6 mg/kg/day of clozapine would produce a steady state plasma concentration of > 350 ng/ml. Twelve patients with schizophrenia by DSM-III-R criteria who were refractory to treatment with standard antipsychotics were treated with clozapine utilizing a 10- to 14-day titration to a target dose of 6 mg/kg/day. The mean (+/- SD) clozapine plasma concentration achieved after 5 days at the target dose was 584 +/- 417 ng/ml. Thus, although the target dose successfully produced therapeutic plasma concentrations for most patients, a wide variation was also apparent.