Effect of the dose regimen on the serum amisulpride concentration and simulation of concentration reference ranges based on population pharmacokinetics

Aims: This study aims to determine the factors associated the large variability and provided the concentrations reference ranges for different dose ranges. Methods A retrospective study was conducted in a psychiatric hospital. The factors associated with the serum amisulpride concentration were examined using multiple linear regression analysis. A comparison of serum amisulpride concentrations among different dose regimens was conducted via analysis of covariance. The amisulpride concentration range for different dosing regimens was simulated using the population pharmacokinetics of Chinese patients with schizophrenia using the Monte Carlo method. Results In total, 472 samples from 291 patients were examined to determine the factors associated with amisulpride concentrations. Multiple linear regression analysis indicated that age and the daily dose were positively correlated with the serum drug concentration, whereas male gender and sampling time before the last administration were negative correlated with its concentration. The serum amisulpride concentration significantly differed among the dose regimens. Using an established amisulpride population pharmacokinetic model, the simulated trough concentrations exceeded 320 ng/mL for most regimens with daily doses greater than 600 mg/day. Conclusion Differences in dose regimens and daily doses contributed to the large variation of the serum amisulpride concentration. The currently recommended reference does not ensure the attainment of appropriate therapeutic concentrations.