Dose-related plasma levels of clozapine: influence of smoking behaviour, sex and age

Abstract

Drug monitoring in psychiatry is of increasing interest due to compliance problems, side effects of psychoactive drugs and thesearch for adequate dosage. In the present study, plasma levels of clozapine, as determined by high performance liquid chromatography, were investigated in 148 patients receiving a daily dose between 12.5 and 700 mg clozapine. Regression analysis revealed a linear relationship between dose and plasma concentrations. Plasma concentrations at a given dose (level divided by dose and body weight) in male patients reached only 69.3% of the concentrations in female patients (Mann-Whitney U Test P<0.001). When the patients were divided into smokers and non-smokers, the corresponding plasma levels were also found to be linearly dose dependent in each of the two groups. However, the average plasma concentration at a given dose was only 81.8% in smokers, compared to non-smokers. This difference was statistically significant (variance analysis P=0.022). Dividing female patients into smokers and non-smokers, the smokers reached nearly the same plasma levels as the non-smokers. Male smoking patients reached average plasma concentrations which were only 67.9% of those of non-smokers. This difference was statisticallysignificant (Mann-Whitney U Test P-0.0083). The plasma levels of the different age groups at a given dose per kg body weight were compared using the Mann-Whitney U Test. Significant differences were found between group 1 (18–26) and group 4 (45–54), (P<0.01) and group 2 (27–35) and group 4 (P<0.01) showing higher plasma levels in the older age group. The present results indicate a considerable variation of clozapine plasma levels at a given dose depending on a number of factors. These factors should be taken into consideration for efficient therapy with the lowest possible dose.