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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。
OBJECTIVE: To establish a population pharmacokinetic model of oral sirolimus in renal transplant recipients, to study the pharmacokinetics of sirolimus in human and to provide theoretical support for the individualized use of drugs. Methods: 111 patients who underwent immunosuppressive therapy with sirolimus after renal transplantation were enrolled in this study. The steady-state plasma concentrations of sirolimus and corresponding laboratory data were collected retrospectively. The NLME pharmacokinetic software establishes a population pharmacokinetic model for sirolimus and analyzes the factors that influence pharmacokinetic parameters. The final model is internally verified using the Bootstrap method and visual predictive inspection. Results: Sirolimus was fitted to a one-compartment kinetic model. The hematocrit was found to have an effect on the clearance rate and the alkaline phosphatase had an effect on the volume of distribution. The final model obtained had a CL / F value of 10.8 L / h and a V / F of 1 011 L. The evaluation results of Bootstrap verification and visual prediction test show that the model prediction result is reliable. Conclusion: In this study, we successfully established a population pharmacokinetic model of sirolimus in renal transplant recipients. The effects of age, weight, sex, combined medication and biochemical parameters on the model were investigated. In order to achieve the rational clinical use of sirolimus for reference.