Study on population pharmacokinetics model of sirolimus in renal transplantation patients
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    Abstract:

    Objective: To construct a population pharmacokinetics(PPK) model of sirolimus in Chinese renal transplantation patients, study the pharmacological characteristics of sirolimus, and provide theory support for personalized drug use. Methods: One hundred and eleven renal transplantation patients, who were orally administrated with sirolimus after transplantation, were enrolled in the study. Steady-state concentrations of sirolimus and related laboratory test results were retrospectively collected. Phoenix NLME was used to perform a population pharmacokinetics model. Influence factors on pharmacokinetic parameter were analyzed. Performance of final model was internally assessed by bootstrapping and visual predictive checking(VPC). Results:A one-compartment model with first-order elimination pharmacokinetics provided the best fitting. In all fixed effects, hematocrit influenced the clearance of sirolimus, alkaline phosphatase influenced volume of distribution. Typical value of CL/F was 10.8 L/h, typical value of V/F was 1011 L. Stability and predictive performance were accepted by bootstrapping and VPC. Conclusion: A PPK model of sirolimus in Chinese renal transplantation patients is successfully established in this study. Effects of weight, age, gender, drug dose, drug combination, liver and kidney function on pharmacokinetic parameter were inspected. It is of great significance for clinical rational drug use of sirolimus.

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张 钰,张宏文,杨 劲,吴延庆,谭若芸,王丽彬,刘 云,王源园,魏继福,王永庆.肾移植患者西罗莫司的群体药代动力学模型研究[J].南京医科大学学报(自然科学版英文版),2017,(9):1193-1199.

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History
  • Received:April 19,2017
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  • Online: September 25,2017
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