基于群体药动学模型的阿立哌唑微球给药方案研究  

Optimizing the dosing regimen of aripiprazole microspheres by population pharmacokinetic modeling and simulation

作　　者：孟庆恒 韩智慧 雷琦 陈斌 尹霞 胡海棠 刘红霞[1] 郑青山[1] 许羚[1] 黄钦 MENG Qingheng;HAN Zhihui;LEI Qi;CHEN Bin;YIN Xia;HU Haitang;LIU Hongxia;ZHENG Qingshan;XU Ling;HUANG Qin(Center for Drug Clinical Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Lizon Pharmaceutical Group Inc.,Zhuhai 519000,Guangdong,China)

机构地区：[1]上海中医药大学药物临床研究中心,上海201203 [2]丽珠医药集团股份有限公司,广东珠海519000

出　　处：《中国临床药理学与治疗学》2025年第4期493-500,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：上海市2017年度“科技创新行动计划”项目(17401970900)。

摘　　要：目的:基于一款新型长效注射用阿立哌唑微球(LZMT05)2项临床试验的血药浓度数据,优选LZMT05的临床剂量和给药方案。方法:196名精神分裂症患者接受LZMT05注射,采集血药浓度数据,并建立群体药动学模型。以口服有效剂量的稳态谷峰浓度区间94.0~534 ng/mL作为治疗窗,设计并模拟多种临床应用场景,选择最优临床治疗方案。结果:LZMT05的药物浓度-时间曲线可用双一级吸收、一级消除的一房室描述。性别、CYP2D6基因型等因素作为协变量引入最终模型。模拟结果显示,稳定使用10 mg阿立哌唑片剂转换为LZMT05350 mg,每4周给药1次,可以使患者体内阿立哌唑浓度始终维持在治疗窗范围内,而且峰谷波动较小。结论:通过群体药动学建模与模拟,本研究优化的LZMT05给药方案能够保持药物暴露水平位于治疗窗内,提示其具备良好的疗效和安全性。AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(PopPK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral aripiprazole.Multiple clinical scenarios were simulated to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order absorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 every 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided optimized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favorable efficacy and safety.

关 键 词：阿立哌唑 微球 群体药动学 建模模拟 

分 类 号：R749.3[医药卫生—神经病学与精神病学] R969.1[医药卫生—临床医学]