Monitoring of plasma clozapine levels and its metabolites in refractory schizophrenic patients

Hui Ching Liu, Wen Ho Chang, Fu Chuan Wei, Shi Kwang Lin, Shih Ku Lin, Michael W. Jann

Research output: Contribution to journalArticle

53 Scopus citations

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.

Original languageEnglish
Pages (from-to)200-207
Number of pages8
JournalTherapeutic drug monitoring
Volume18
Issue number2
DOIs
StatePublished - 12 Apr 1996

Keywords

  • Clozapine
  • Clozapine metabolites
  • Schizophrenia

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