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

Abstract

What is already known about this subject • Plasma concentrations of clozapine (CLZ) and its active metabolite vary considerably at a given dosage. • A number of patient-related factors have been reported to increase the variability of plasma CLZ concentrations, with gender, age and smoking behaviour representing some of the more important contributing variables • However, results of previous studies concerning these factors have been inconsistent and most studies were conducted in western populations. What this study adds • Using this ethnically unique, relatively large sample, we replicated some findings in western populations, including large interindividual variability of plasma CLZ concentrations, significant effects of gender on plasma CLZ concentrations. • Female patients had significantly higher levels than males and no significant differences in plasma CLZ concentrations were observed between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher. 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 (≤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 ≤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.