GENDER DIFFERENCES IN PLASMA CLOZAPINE LEVELS AND ITS METABOLITES IN SCHIZOPHRENIC-PATIENTS

Forty refractory schizophrenic patients (21 females and 19 males) part icipated in a fixed-dose study with clozapine, After a 6-week trial of haloperidol and a 1-week washout time period, non-responding patients were placed on clozapine and the dosage titrated up to 400 mg/day for the next 5 weeks. Plasma clozapine levels and its two metabolites des methylclozapine (DCLOZ) and clozapine N-oxide (CNO) were measured at w eeks 2, 4 and 6. Blood samples were obtained 10-12 h post-evening dose and prior to the morning dose. Clozapine and its metabolites were ass ayed by HPLC with UV detection. Patients were assessed for clinical re sponse with the Brief Psychiatric Rating Scale (BPRS) at baseline and at weeks 2, 4 and 6. BPRS scores were also divided into positive (+) a nd negative(-) symptoms subscales. Plasma clozapine and DCLOZ levels w ere significantly lower in males. Plasma CNO levels were slightly lowe r in males but it was not statistically significant. Decreased total B PRS, (+) and (-) symptoms subscale scores occurred during the study fo r both gender groups. A greater magnitude of change for the (-) sympto m subscale score was observed in the male group. Gender was not a sign ificant factor in the incidence or severity of side-effects. (C) 1997 John Wiley & Sons, Ltd.