title: Monitoring of plasma clozapine levels and its metabolites in refractory schizophrenic patients.
abstract: Plasma concentrations of clozapine and its metabolites desmethylclozapine and clozapine N-oxide were measured in 61 patients with refractory schizophrenia. Before the initiation of clozapine, each patient was given haloperidol (HL) up to 60 mg/day for at least 4 weeks without improvement. Patients were then given a fixed dose of clozapine 400 mg/day. Patients were assessed with the Brief Psychiatric Rating Scale (BPRS) at baseline before HL therapy, at the end of HL at 6 weeks, before clozapine, and after 6 weeks of clozapine therapy. Clozapine and its metabolites were measured by high-performance liquid chromatography with ultraviolet detection. The mean plasma concentrations of clozapine, desmethylclozapine, and clozapine N-oxide were 598 +/- 314, 281 +/- 140, and 90 +/- 29 ng/ml, respectively. The mean decrease in the total BPRS scores from baseline clozapine to the 6-week treatment period was 11 +/- 4. Clinical improvement was noted to occur in most patients with clozapine plasma levels > 300 ng/ml. Improvement diminished in patients with clozapine plasma levels > 700 ng/ml. The most common adverse effects were sedation and hypersalivation. Significant correlations between plasma clozapine concentrations and adverse side effects were not found.
authors.affiliation: Laboratory of Biological Psychiatry, Taipei City Psychiatric Center, Taiwan, Republic of China.
authors.forename: H C
authors.initials: HC
authors.lastname: Liu
authors.forename: W H
authors.initials: WH
authors.lastname: Chang
authors.forename: F C
authors.initials: FC
authors.lastname: Wei
authors.forename: S K
authors.initials: SK
authors.lastname: Lin
authors.forename: S K
authors.initials: SK
authors.lastname: Lin
authors.forename: M W
authors.initials: MW
authors.lastname: Jann
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003024:Clozapine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; C058272:norclozapine; D003024:Clozapine; D006220:Haloperidol