Clozapine and metabolites: concentrations in serum and clinical findings during treatment of chronically psychotic patients.

摘要: Clozapine (CLZ) and metabolites norclozapine clozapine-N-oxide were assayed with a new, sensitive (2 pmol), selective method in 68 serum samples from 44 psychotic subjects, 20 to 54 years old, ill 16 years, treated CLZ for 2.2 (currently at 294 mg, 3.4 mg/kg daily). levels averaged 239 ng/ml (0.73 microM; 92 per dose) or 48% of total analytes (norclozapine = 41% [91% CLZ] 11%); metabolite highly correlated (rs 0.9), varied daily dose 0.7). Sampling twice yielded similar within-subject analyte (r 0.8 0.9; difference 24% 33%). Range variance narrowed when expressed weight-corrected (ng/ml mg/kg). Levels 40% higher nonsmoking women than men, despite 60% lower milligram kilogram women, did not vary by diagnosis age this limited sample. Fluoxetine increased 60%; valproate had less effect. Patients rated treatment very positively; observer-assessed benefits typically more moderate. Common late side effects sialorrhea (80%), excess sedation (58%), obesity (55% > 200 lb), mild tachycardia (51%), constipation (32%), enuresis (27%); there no seizures leukopenia. There was little evident relationship drug level current clinical measures effect risks.