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

Ther Drug Monit. 1996 Apr;18(2):200-7. doi: 10.1097/00007691-199604000-00015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / blood*
  • Antipsychotic Agents / therapeutic use
  • Chromatography, High Pressure Liquid / methods
  • Clozapine / adverse effects
  • Clozapine / analogs & derivatives*
  • Clozapine / blood*
  • Clozapine / therapeutic use
  • Female
  • Haloperidol / adverse effects
  • Haloperidol / blood
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy


  • Antipsychotic Agents
  • norclozapine
  • Clozapine
  • Haloperidol