Wuzhi Capsule Dosage Affects Tacrolimus Elimination in Adult Kidney Transplant Recipients, as Determined by a Population Pharmacokinetics Analysis

Abstract

Purpose In this study, we aimed to establish a tacrolimus population pharmacokinetic model and better understand the drug-drug interaction between Wuzhi capsule and tacrolimus in Chinese renal transplant recipients. Patients and Methods We performed a population pharmacokinetic analysis using a non-linear mixed-effects model to determine the suitable Wuzhi capsule dose in combination with tacrolimus. Data on 1378 tacrolimus steady-state concentrations were obtained from 142 patients who received kidney transplant in Changhai Hospital and Huashan Hospital. Demographic characteristics, laboratory tests, genetic polymorphisms, and co-medications were evaluated. Results The one-compartment model best described data. Our final model identified creatinine clearance rate, hematocrit, Wuzhi capsule dose, CYP3A5*3 genetic polymorphisms, and tacrolimus daily dose as significant covariates for tacrolimus clearance, with the value of 14.4 L h−1, and the between-subject variability (BSV) was 25.4%. The Wuzhi capsule showed a dose-dependent effect on tacrolimus pharmacokinetics, demonstrating a stronger inhibitory effect than inductive effect. Conclusion Our model can accurately describe population pharmacokinetics of tacrolimus when combined with different doses of Wuzhi capsule. Additionally, this model can be used for individualizing tacrolimus dose following kidney transplantation.