Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model
Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model
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DOI：
10.1016/j.apsb.2020.04.007
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发表时间：
2020-07-01
影响因子：
14.5
通讯作者：
Liu, Dongyang
中科院分区：
文献类型：
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作者：
Cui, Cheng;Zhang, Miao;Liu, Dongyang
氯喹(CQ)磷酸已被建议在临床上有效的治疗冠状病毒病2019年(新冠肺炎)。为了建立基于生理的药物动力学(PBPK)模型来预测CQ的组织分布，并将其应用于优化给药方案，根据动物数据外推药物分布的参数，建立了预测CQ组织分布的PBPK模型。通过主动运输机制模拟了随时间积累的生理特征。基于PBPK模拟结合已知的临床暴露反应关系，提出了几种给药方案。该模型还得到了中国新冠肺炎患者的临床数据的验证。该模型能够深入描述CQ在几个关键器官(肺、心、肝和肾)的药代动力学，并被用于设计急性新冠肺炎患者(第1天：750 mg BID，第2-5天：500 mg BID，CQ磷酸盐)、中度新冠肺炎患者(第1天：750 mg和500 mg BID，第2-3天：500 mg BID，第4-5天：250 mg BID，CQ磷酸盐)以及其他易感人群(如肾、肝损害和老年患者，1-5天：250 mg BID，CQ磷酸盐)的给药策略。CQ磷酸盐)。成功地建立了CQ的PBPK模型，以优化新冠肺炎患者的给药方案。(C)中国医学科学院中国药学会、药物所2020年。爱思唯尔B.V.制作和主办。
Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 ( COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposureeresponse relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2 -5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2 -3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (e.g., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.