蒙特卡洛模拟优化精神分裂症患者氨磺必利的维持给药方案

Optimizing maintenance dosing regimens of amsulpride in schizophrenics using Monte Carlo simulation

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(C_(ss))及其推荐血药浓度参考范围100~600 ng·m L^(–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,C_(ss)分布于100~600 ng·m L^(–1)的PTA>90%。当日剂量≥1050 mg时,C_(ss)很可能大于600 ng·m L^(–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48.10~1032.03 ng·m L^(–1),均值为(466.64±284.10)ng·m L^(–1)。结论:MC_S可预测中国精神分裂症患者氨磺必利的C_(ss)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·m L^(–1)具有合理性。

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(Css)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≥1050 mg,Css was likely to surpass 600 ng·mL^(–1)(simulation probability≥75.61%).Blood concentration of amisulpride at a conventional dose in 24 samples was 48.10−1032.03 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.