Aim.The aim of this study was to establish population pharmacokinetic models of tacrolimus in Chinese adult liver transplantation\r\npatients. Methods. Tacrolimus dose and concentration data (n = 435) were obtained from 47 Chinese adult liver transplant\r\nrecipients, and the data were analyzed using a nonlinear mixed-effectmodeling (NONMEM) method. Results.The structuralmodel\r\nwas a two-compartment model with first-order absorption. The typical population values of tacrolimus for the pharmacokinetic\r\nparameters of apparent clearance (CL/F), apparent distribution volume of the central compartment (V2/F), intercompartmental\r\nclearance (Q/F), apparent distribution volume of the peripheral compartment (k3/F), and absorption rate (ka) were 11.2 L/h, 406 L,\r\n57.3 L/h, 503 L, and 0.723 h-1, respectively.The interindividual variabilities of these parameters were 16.2%, 163%, 19.7%, 199%, and\r\n74.3%, respectively, and the intraindividual variability of observed concentration was 26.54%. The covariates retained in the final\r\nmodels were postoperative days (POD) and dosage per day (DOSE) on CL/??. Conclusion. Population pharmacokinetic models of\r\ntacrolimus were developed in Chinese adult liver transplant patients. These results could provide the interpretation of the outcome\r\nof pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy.
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