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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Zhang Yu, Zhang Hongwen, Yang Jin, Wu Yanqing, Tan Ruoyun, Wang Libin, Liu Yun, Wang Yuanyuan, Wei Jifu, Wang Yongqing. Study on population pharmacokinetics model of sirolimus in renal transplantation patients[J].,2017,(9):1193-1199.

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