Population pharmacokinetics and individual analysis of daptomycin in kidney transplant recipients
Population pharmacokinetics and individual analysis of daptomycin in kidney transplant recipients
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达托霉素在肾移植受者体内的群体药代动力学及个体分析
DOI：
10.1016/j.ejps.2021.105818
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发表时间：
2021
影响因子：
4.6
通讯作者：
Huang Hongfeng
中科院分区：
文献类型：
--
作者：
Lou Yan;Liu Yi-xi;Wang Jiali;Cai Liefeng;He Lingjuan;Yang Xi;Xu Haoxiang;He Xiaoying;Yang Xiuyan;Wei Chunchun;Huang Hongfeng
背景：关于达托霉素在肾移植患者中的群体药代动力学（PPK）知之甚少。本研究建立了达托霉素在中国肾移植患者和受试者体内的药动学模型，并分析了影响达托霉素药动学参数的重要因素。方法：研究人群包括49例肾移植患者，537个达托霉素浓度。采用非线性混合效应模型、二室结构模型和混合残差模型建立了达托霉素的PPK模型。最终模型的稳定性和预测能力进行了评估的基础上引导，视觉预测检查和归一化的预测分布误差。结果如下：肾小球滤过率（GFR）和总体重显著影响清除率，体重影响中心分布容积。群体的平均清除率为0.316 L/h，中心分布容积为6.04 L，房室间清除率为2.31 L/h，外周分布容积为2.46 L。基于建立的模型和曲线下面积（AUC 0 - 24 h）/最小抑制浓度（MIC）≥666的目标，我们根据肾移植患者的肾功能和体重制定了推荐的给药方案。当GFR为15、30、45、60、75和90 ml/min/1.73 m2时，每日剂量分别为4.0±0.31、4.7±0.36、5.1 ± 0.40、5.5±0.43、5.8±0.45和6.1±0.48 mg/kg。结论：本研究为肾移植受者达托霉素的个体化给药提供了参考，为提高达托霉素的治疗效果和降低毒副作用提供了宝贵的资源。
Background: Little is known about the population pharmacokinetics (PPK) of daptomycin in kidney transplant patients. The present study established a pharmacokinetic model for daptomycin in kidney transplant patients in China and examinee the important factors affecting the pharmacokinetic parameters of daptomycin. Methods: The study population included 49 kidney transplant patients with 537 daptomycin concentrations. The PPK model of daptomycin was developed using a nonlinear mixed-effects model, a two-compartment structural model, and a mixed residual error model. The stability and predictive ability of the final model were evaluated based on bootstrapping, visual prediction checks and normalized prediction distribution errors. Results: Glomerular filtration rate (GFR) and total body weight significantly affected clearance, and body weight influenced the central volume of distribution. The average clearance of the population was 0.316 L/h, the central volume of distribution was 6.04 L, the intercompartmental clearance was 2.31 L/h, and the peripheral volume of distribution was 2.46 L. Based on the established model and the target of area under curve (AUC0-24h)/ minimum inhibition concentration (MIC) ≥666, we developed a recommended dose regimen for kidney transplant patients according to their renal function and weight. The daily doses were 4.0±0.31, 4.7±0.36, 5.1±0.40, 5.5±0.43, 5.8±0.45, and 6.1±0.48 mg/kg when the GFRs were 15, 30, 45, 60, 75, and 90 ml/min/1.73 m2, respectively. .Conclusion: This study provides a reference for individualized daptomycin administration in kidney transplant recipients, and it is a valuable resource for improving the treatment effect and reducing the toxic effects of daptomycin.