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

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57 Scopus citations


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
Issue number2
StatePublished - 12 Apr 1996


  • Clozapine
  • Clozapine metabolites
  • Schizophrenia


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