Steady-state Pharmacokinetics of Clozapine in Refractory Schizophrenic Saudi Arabian Patients

Abstract

The steady-state pharmacokinetics of the atypical antipsychotic drug clozapine in schizophrenic Saudi Arabian patients was studied and correlated with the clinical outcome. Twenty-six schizophrenic patients were given clozapine over a period of 2–41 months. The daily dose ranged from 100 to 700 mg, and the frequency of administration varied from 1 to 2 times daily. A blood sample was collected from each patient at the midpoint of the dosing interval and was repeated on different days in six randomly selected patients to establish the steady-state condition. The concentration of clozapine in plasma (Css) was measured by HPLC with UV detection at 250 nm using C18 bonded SepPak cartridges for sample preparation. The apparent oral clearance (CLp.o.) was calculated from the equation: CLp.o. = dose/tCss where t is the time between two consecutive doses. The effectiveness of the treatment was evaluated by the standard Positive and Negative Syndrome Scale (PANSS). The mean ± s.d. steady-state concentration (Css) was 491 ± 299 ng mL−1 There were no significant differences in Css or any of the pharmacokinetic parameters studied between the 11 patients who responded positively to the treatment and the 15 patients who responded negatively. These results do not support the hypothesis that there is a positive correlation between higher plasma concentrations and positive response from clozapine in Saudi Arabian patients.