Olanzapine Plasma Concentrations After Treatment With 10, 20, and 40 mg/d in Patients With Schizophrenia: An Analysis of Correlations With Efficacy, Weight Gain, and Prolactin Concentration

Abstract

Objectives of the study were to evaluate the relationship between olanzapine plasma concentrations and efficacy, prolactin, and weight and to assess effects of smoking, sex, and race on the pharmacokinetic characteristics of oral olanzapine up to 40 mg/d. Patients were randomly allocated to olanzapine 10, 20, or 40 mg/d for 8 weeks. Olanzapine concentrations in 634 samples from 380 patients were analyzed. Mean sample collection time was approximately 15 hours after dose for all groups. Mean olanzapine concentrations were 19.7 +/- 11.4, 37.9 +/- 22.8, and 74.5 +/- 43.7 ng/mL for 10-, 20-, and 40-mg doses, respectively. Olanzapine concentration and Positive and Negative Syndrome Scale improvement were not significantly correlated. Change in both weight and prolactin showed significant dose response. Prolactin concentration was correlated with olanzapine concentration (r = 0.46, P < 0.001). No significant correlation between olanzapine concentration and weight change was observed. Olanzapine concentrations were lower in self-reported smokers (16.5 +/- 9.6, 34.2 +/- 20.8, and 60.9 +/- 34.6 ng/mL) than in self-reported nonsmokers (25.6 +/- 12.3, 43.4 +/- 24.7, and 113.2 +/- 44.0 ng/mL) for 10-, 20-, and 40-mg doses, respectively (P </= 0.022). In the 40-mg group only, African Americans had a lower mean olanzapine concentration than whites (65.6 +/- 44.1 and 84.8 +/- 44.1 ng/mL, respectively, P = 0.048). Women had numerically but not significantly higher mean olanzapine concentrati…