Population Pharmacokinetics of Tacrolimus in Patients with Nephrotic Syndrome

OBJECTIVE To investigate a population pharmacokinetics characteristic of tacrolimus in patients with nephrotic syndrome by using nonlinear mixed effect model NONMEM. METHODS Totally 246 trough concentrations were retrospectively collected from 51 patients with nephrotic syndrome who received tacrolimus. Using age, sex, body weight, daily dose of tacrolimus, liver and kidney function and co-therapy medications as covariates, a one-compartment model with first order absorption and elimination was used to analyze the data, and the model was assessed by using bootstrap and normal prediction distribution error. RESULTS The tacrolimus of apparent clearance(CL/F) and apparent volume of distribution(V/F) was 13.9 L·h^-1 and 382 L, respectively. Daily dose of tacrolimus(DD, mg·d^-1), hematokrit(HCT) and co-administration of Wuzhi capsule had a significant effect on the CL/F. The model evaluation showed that the model and the estimated parameters were reliable and stable. The final model of CL/F was CL/F=13.9×0.668^WZ×(DD/2)^0.354×(HCT/0.394)^-0.522. When combined with Wuzhi capsule, WZ was 1, whereas was 0. CONCLUSION The population pharmacokinetics model of tacrolimus in nephrotic syndrome patients can better estimate population and individual pharmacokinetic parameters, which can provide relevant reference of individualized dosing regimen of tacrolimus.