肾移植患者西罗莫司的群体药代动力学模型研究

发布时间：2018-05-18 00:36

本文选题：西罗莫司 + 肾移植　；参考：《南京医科大学学报(自然科学版)》2017年09期

【摘要】：目的 :建立肾移植患者口服西罗莫司片的群体药代动力学模型,研究西罗莫司在人体内的药动学特点,为实施个体化用药提供理论支持。方法:以111例肾移植术后采用西罗莫司进行免疫抑制治疗的患者为研究对象,回顾性收集患者常规监测的西罗莫司稳态血药浓度及相应的实验室检查数据,运用Phoenix NLME药动学软件建立西罗莫司的群体药动学模型,分析影响药动学参数的因素。最终模型采用Bootstrap法和可视化预测检查进行内部验证。结果:西罗莫司符合一级消除动力学一室模型。发现红细胞比容对清除率有影响,碱性磷酸酶对分布容积有影响,获得的最终模型CL/F值为10.8 L/h,V/F为1 011 L。Bootstrap验证和可视化预测检查的评价结果表明模型预测结果可靠。结论 :本研究成功建立了肾移植患者西罗莫司的群体药动学模型,考察了年龄、体重、性别、合并用药以及各生化指标对模型的影响,为实现西罗莫司的临床合理用药提供参考。
[Abstract]:Aim: to establish a population pharmacokinetic model of sirolimus tablets for renal transplantation and to study the pharmacokinetic characteristics of sirolimus in human body in order to provide theoretical support for individualized drug use. Methods: 111 patients who received sirolimus immunosuppressive therapy after renal transplantation were studied. The serum concentrations of sirolimus and the corresponding laboratory data were collected retrospectively. A population pharmacokinetic model of sirolimus was established with Phoenix NLME software and the factors affecting pharmacokinetic parameters were analyzed. The final model is verified by Bootstrap method and visual prediction check. Results: sirolimus was in accordance with one compartment model of one-compartment elimination kinetics. It was found that the specific volume of erythrocyte had an effect on the clearance rate, and alkaline phosphatase had an effect on the distribution volume. The final model CL/F value was 10.8 L / h ~ (-1) V / F = 1 011 L.Bootstrap. The evaluation results showed that the model prediction results were reliable. Conclusion: a population pharmacokinetic model of sirolimus was successfully established in this study. The effects of age, body weight, sex, combined medication and biochemical indexes on the model were investigated. To provide a reference for the clinical rational use of sirolimus.
【作者单位】：南京医科大学第一附属医院药学部;中国药科大学药学院;南京医科大学第一附属医院泌尿外科;
【基金】：南京市科技发展指导性计划(2016YX006) 南京药学会—常州四药医院药学科研基金
【分类号】：R969.1

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