目的:运用蒙特卡洛模拟(Monte Carlo simulation,MCs)优化精神分裂症患者氨磺必利的维持给药方案.方法:基于已发表的氨磺必利在精神分裂症患者的群体药动学数据,利用MCs预测其在不同给药方案下稳态血药浓度(Css)及其推荐血药浓度参考范围100～600 ng·mL-1的达标概率(probability of target attainment,PTA),结合临床血药浓度监测结果进行验证.结果:当氨磺必利的给药方案分别为350～400 mg qd,150～300 mg bid,100～200 mg tid,Css分布于100～600 ng·mL-1的PTA＞90％.当日剂量≥1 050 mg时,Css很可能大于600ng·mL-1(模拟概率≥75.61％).24份常规剂量下氨磺必利血药浓度结果为48.10～1 032.03 ng·mL-1,均值为(466.64±284.10)ng·mL-1.结论:MCs可预测中国精神分裂症患者氨磺必利的Css及其处于治疗浓度参考范围的概率;根据临床治疗情况,常规剂量下将氨磺必利参考浓度范围设定为100～600 ng·mL-1具有合理性.
Optimizing maintenance dosing regimens of amsulpride in schizophrenics using Monte Carlo simulation
OBJECTIVE To optimize the maintenance dosing regimen of amisulpride in schizophrenics using Monte Carlo simulations(MCs).METHODS Based upon the published population pharmacokinetic(PPK)data of amisulpride in schizo-phrenics,using MCs to predict its steady-state plasma concentration(Cs)and its recommended blood concentration reference range of 100-600 ng·mL-1 under different dosage regimens.Probability of target attainment(PTA)was applied along with monitoring clinical blood drug concentrations for verification.RESULTS When amisulpride was 350-400 mg qd,150-300 mg bid and 100-200 mg tid,PTA value of Css was＞90％in the range of 100-600 ng·mL-1.At a daily dose ≥1 050 mg,Cs was likely to surpass 600 ng·mL-1(simulation probability ≥75.61％).Blood concentration of amisulpride at a conventional dose in 24 samples was 48.10-1 032.03 ng·mL-1 with an average value of(466.64±284.10)ng·mL-1.CONCLUSION MCs may predict Css of amisulpride in Chinese schizophrenics.According to clinical treatment,it is reasonable to set the reference concentra-tion range of amisulpride at 100-600 ng·mL-1 under a conventional dose.
amisulprideMonte Carlo simulationsteady-state plasma concentrationschizophrenia
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