Clozapine, norclozapine plasma levels, their sum and ratio in 50 psychotic patients: influence of patient-related variables

Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr;26(3):473-80. doi: 10.1016/s0278-5846(01)00291-3.


Steady-state plasma concentrations of clozapine and norclozapine, its major metabolite, as well as their sum and ratio (norclozapine/clozapine), were evaluated in 50 in- and outpatients taking clozapine and naturalistically recruited. Drug plasma concentrations were measured by means of a reversed-phase high-performance liquid chromatography (RPLC) method with an ultraviolet detection. Daily doses (milligrams per kilogram of body weight) of clozapine correlated positively with clozapine plasma parameters, except with the norclozapine/clozapine ratio, in all patients. When the patients were divided in subgroups with respect to gender, the corresponding plasma concentrations were no longer dose-related in men. A lack of significant correlation was observed also in patients (n=23) co-treated with typical neuroleptics. Conversely, dose-concentration correlations were significant in either smoker or nonsmoker patients. No significant relationship between body weight and clozapine plasma parameters was reported. Further, we observed (1) a trend towards higher medians of clozapine or total analytes in women than those reported in men (P=.09 and .07); (2) no significant difference in plasma levels obtained in subjects younger than 34 years and subjects 34 years old or older; (3) a trend towards higher norclozapine and clozapine plus norclozapine levels (P=.05 and .08) in nonsmoker than smoker patients; (4) no significant difference between clozapine plasma parameters measured in patients co-medicated with typical neuroleptics and in patients receiving clozapine alone.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Clozapine / analogs & derivatives*
  • Clozapine / blood*
  • Clozapine / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Patients / statistics & numerical data
  • Psychotic Disorders / blood*
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / psychology
  • Sex Factors
  • Smoking / blood
  • Statistics, Nonparametric


  • norclozapine
  • Clozapine