Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia

Br J Clin Pharmacol. 2007 Jul;64(1):49-56. doi: 10.1111/j.1365-2125.2007.02852.x. Epub 2007 Feb 12.

Abstract

Aim: To study the relationship between age, gender, cigarette smoking and plasma concentrations of clozapine (CLZ) and its metabolite, norclozapine (NCLZ) in Chinese patients with schizophrenia.

Methods: Data from a therapeutic drug monitoring programme were analysed retrospectively. One hundred and ninety-three Chinese inpatients with schizophrenia were assessed using clinical data forms. Steady-state plasma concentrations of CLZ and NCLZ were assayed using high-performance liquid chromatography. Comparisons of dosage and plasma CLZ concentrations were undertaken between males (n = 116) and females (n = 77), younger (<or=40 years, n = 82) and older patients (>40 years, n = 111) and current male smokers (n = 50) and nonsmokers (n = 66).

Results: (i) Plasma CLZ concentrations demonstrated large interindividual variability, up to eightfold at a given dose; (ii) there were significant effects of gender on plasma CLZ concentrations (relative to dose per kg of body weight) with female patients having significantly higher concentrations than males (30.09 +/- 24.86 vs. 19.87 +/- 3.55 ng ml(-1) mg(-1) day(-1) kg(-1); P < 0.001); (iii) there were no significant differences in plasma CLZ concentrations between those patients <or=40 years old and those >40 years; and (iv) there were no significant differences in plasma CLZ concentrations between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher.

Conclusions: Plasma CLZ concentrations vary up to eightfold in Chinese patients. Among the patient-related factors investigated, only gender was significant in affecting CLZ concentrations in Chinese patients with schizophrenia, with female patients having higher levels.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / blood*
  • Antipsychotic Agents / therapeutic use
  • Asian People
  • Clozapine / analogs & derivatives
  • Clozapine / blood*
  • Clozapine / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Schizophrenia / blood
  • Schizophrenia / drug therapy*
  • Sex Factors*
  • Smoking / metabolism

Substances

  • Antipsychotic Agents
  • norclozapine
  • Clozapine