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

摘要

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 (V2/F), intercompartmental clearance (Q/F), apparent distribution volume of the peripheral compartment (V3/F), and absorption rate (ka) 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) onCL/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.