Full length original paper clinical study
Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients

https://doi.org/10.1016/S0278-5846(98)00035-9Get rights and content

Abstract

  • 1.

    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.

    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.

    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.

    4. DCLOZ plasma concentrations were detected in all patients upon clozapine administration. Upon CNO administration, only one patient had detectable plasma DCLOZ levels.

  • 5.

    5. The interconversion process of clozapine and CNO could partially account for the wide interpatient variability reported for clozapine plasma concentrations in schizophrenic patients.

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