Modeling and simulation for individualized therapy of amisulpride in Chinese patients with schizophrenia:focus on inter interindi⁃vidual variability,therapeutic reference range and laboratory alert level  

作　　者：HUANG Shan-qing LI Lu WANG Zhan-zhang XIAO Tao LI Xiao-lin LIU Shu-jing ZHANG Ming LU Hao-yang WEN Yu-guan SHANG De-wei 

机构地区：[1]The Affiliated Brain Hospital of Guangzhou Medical University,Guangzhou 510370,China

出　　处：《中国药理学与毒理学杂志》2021年第9期661-662,共2页Chinese Journal of Pharmacology and Toxicology

摘　　要：OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese patients with schizophrenia was built based on therapeu⁃tic drug monitoring data to guide individualized therapy.METHODS Plasma concentration data(330 measurements from 121 patients)were ana⁃lyzed using a nonlinear mixed-effects model⁃ing approach with first-order conditional estima⁃tion with interaction(FOCE I).The concentra⁃tions of amisulpride were detected by HPLC-MS/MS.Age,weight,sex,combination medication history and renal function status were evaluated as main covariates.The model was internally val⁃idated using goodness-of-fit,bootstrap and nor⁃malized prediction distribution error.Recom⁃mended dosage regimens for patients with key covariates were estimated on the basis of Monte Carlo simulations and the established model.RESULTS A one-compartment model with first-order absorption and elimination was found to adequately characterize amisulpride concentra⁃tion in Chinese patients with schizophrenia.The population estimates of the apparent volume of distribution(V/F)and apparent clearance(CL/F)were 12.7 L and 1.12 L·h-1,respectively.Age sig⁃nificantly affected the clearance of amisulpride and the final model was as follow:CL/F=1.04×(AGE/32)-0.624(L·h-1).To avoid exceeding the lab⁃oratory alert level(640μg·L-1),the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg per day for patients aged 60 years,800 mg per day for those aged 40 years and 1200 mg per day for those aged 20 years,respectively.CON⁃CLUSION Dosage optimization of amisulpride can be carried out according to age to reduce the risk of adverse reactions.The model can be used as a suitable tool for designing individual⁃ized therapy for Chinese patients with schizo⁃phrenia.

关 键 词：AMISULPRIDE population pharmacoki⁃netics therapeutic drug monitoring modeling and simulation individualized therapy 

分 类 号：R749.3[医药卫生—神经病学与精神病学]