Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients

Wen Ho Chang, Shih Ku Lin, Hsien Yuan Lane, Fu Chuan Wei, Wei Herng Hu, Y. W.Francis Lam, Michael W. Jann

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


1. To characterize the interconversion process between clozapine and its metabolite clozapine N-oxide (CNO), eight healthy male schizophrenics were administered a single dose of clozapine or CNO in a randomized crossover manner. 2. Using a general pharmacokinetic model for the interconversion process, the mean total clearances of clozapine and CNO were 28.45 L/hr and 45.30 L/hr, respectively. These values were similar to the values obtained by the usual model-independent method of pharmacokinetic analysis. 3. When administered clozapine, mean CNO plasma concentrations of 17.7±16.4 ng/ml were slightly lower than the other clozapine metabolite - desmethylclozapine (DCLOZ) plasma levels of 24.4±8.6 ng/ml at the 12 hour time point. When CNO was administered, plasma concentrations at the 12 hour time point of clozapine were twice the amount of CNO (28.1±8.9 ng/ml vs 14.4±8.8 ng/ml). 4. DCLOZ plasma concentrations were detected in all patients upon clozapine administration. Upon CNO administration, only one patient had detectable plasma DCLOZ levels. 5. The interconversion process of clozapine and CNO could partially account for the wide interpatient variability reported for clozapine plasma concentrations in schizophrenic patients.

Original languageEnglish (US)
Pages (from-to)723-739
Number of pages17
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Issue number5
StatePublished - Jul 1 1998


  • Clozapine
  • Clozapine N-oxide concentrations
  • Reversible metabolism

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry


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