title: The Population Pharmacokinetic Models of Tacrolimus in Chinese Adult Liver Transplantation Patients.
abstract: 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.
authors.affiliation: Department of Pharmacy, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Basic Medical College, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Rao
authors.affiliation: Department of Liver Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.affiliation: Basic Medical College, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Liver Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Sun