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The Population Pharmacokinetic Models of Tacrolimus in Chinese Adult Liver Transplantation Patients.

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单位: [1]Department of Pharmacy, Tianjin First Central Hospital, Tianjin 300192, China. [2]Basic Medical College, Tianjin Medical University, Tianjin 300070, China. [3]Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin 300192, China. [4]Department of Liver Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
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Aim. The aim of this study was to establish population pharmacokinetic models of tacrolimus in Chinese adult liver transplantation patients. Methods. Tacrolimus dose and concentration data (n = 435) were obtained from 47 Chinese adult liver transplant recipients, and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. Results. The structural model was a two-compartment model with first-order absorption. The typical population values of tacrolimus for the pharmacokinetic parameters of apparent clearance (CL/F), apparent distribution volume of the central compartment (V 2/F), intercompartmental clearance (Q/F), apparent distribution volume of the peripheral compartment (V 3/F), and absorption rate (k a ) were 11.2 L/h, 406 L, 57.3 L/h, 503 L, and 0.723 h(-1), respectively. The interindividual variabilities of these parameters were 16.2%, 163%, 19.7%, 199%, and 74.3%, respectively, and the intraindividual variability of observed concentration was 26.54%. The covariates retained in the final models were postoperative days (POD) and dosage per day (DOSE) on CL/F. Conclusion. Population pharmacokinetic models of tacrolimus were developed in Chinese adult liver transplant patients. These results could provide the interpretation of the outcome of pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy.

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第一作者单位: [1]Department of Pharmacy, Tianjin First Central Hospital, Tianjin 300192, China.
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