Effects of age and sex on olanzapine plasma concentrations

Age and sex may influence both efficacy and side effects of second-generation antipsychotics. Women and elderly patients tend to have a higher prevalence for several side effects. Higher plasma levels in these groups of patients may be one reason. We studied the hypothesis that steady-state olanzapine plasma concentrations depend on age and sex. Sixty-seven inpatients on stable olanzapine dose were referred to routine therapeutic drug monitoring of olanzapine. Plasma levels were determined by high-performance liquid chromatography with electrochemical detection. Obtained data were then analyzed by analysis of covariance. Olanzapine plasma levels showed a marked sex difference with significantly higher mean concentrations in female patients (adjusted mean concentrations, 18.5 ng/mL for men and 31.7 ng/mL for women; P = 0.003). On average, the weight-corrected concentration/dose ratios shown by women were 33.5% higher than those shown by men, irrespective of age. Regarding the effect of age, weight-corrected concentration/dose ratios increased by an average of 9.4% per decade of life. All results were adjusted for smoking. Comedication did not significantly influence these results. In conclusion, age and sex are important variables to consider when prescribing olanzapine for women and in the elderly.