Age, Sex, and Comedication Effects on the Steady-State Plasma Concentrations of Amisulpride in Chinese Patients with Schizophrenia

Background:Amisulpride, a second-generation atypical antipsychotic drug, was first marketed in Europe in the 1990s. This study aimed to provide a reference for the clinical application of amisulpride. The effects of age, sex, or specific comedications on amisulpride concentrations in Chinese patients with schizophrenia in the real world were investigated.Methods:A retrospective study was conducted of data on amisulpride based on the therapeutic drug monitoring service database at the Zigong Affiliated Hospital of Southwest Medical University.Results:Based on the inclusion criteria, 195 plasma samples from 173 patients (67.05% female and 32.95% male patients) were included for in-depth analysis. The median daily dose of amisulpride was 400 mg/d, median plasma concentration was 457.50 ng/mL, and median concentration/dose (C/D) ratio was 1.04 ng/mL/mg/d. The daily dose of amisulpride positively correlated with measured steady-state plasma concentrations. A significant difference was observed in the subgroup analysis of the combination with valproic acid, zopiclone, or aripiprazole on plasma concentrations. Combining amisulpride with these drugs increased the C/D ratios by 0.56-, 2.31-, and 0.77-fold, respectively. After adjusting for age, the median C/D ratio was found to be significantly different between female and male patients. However, no significant differences in daily dose, plasma concentration, and C/D ratio were noted with respect to sex and age of the patients.Conclusions:Sex differences were inferred for the first time in this study, with differential effects on daily dose, steady-state plasma concentration, and C/D ratio associated with the population. In the included study samples, blood concentrations were distributed in the range of 223.25-823.55 ng/mL, which perhaps needs to be evaluated in line with the reference range of ammonia-sulfur ratios in the Chinese population.