Effects of CYP3A5, ABCB1 and POR*28 polymorphisms on pharmacokinetics of tacrolimus in the early period after renal transplantation.

1. We aimed to establish a population pharmacokinetic (PK) model of tacrolimus and identify clinical covariates, especially the genetic polymorphisms of CYP3A5, ABCB1 and POR*28 that affected the PK to prevent fluctuation in the trough concentration of tacrolimus during the early period after renal transplantation. 2. Tacrolimus trough concentration, clinical data and CYP3A5/ABCB1/POR28 genotypes were retrospectively collected from 234 kidney transplant recipients during the first month post-transplantation. The population PK model was built using the non-linear mixed effects modeling software NONMEM. Dosing simulation was performed based on the final model. 3. A one-compartment model with first-order absorption and elimination was used to characterize the PK of tacrolimus. Among the genotypes, only CYP3A5 genotype was confirmed to have clinical significance. The final model describing CL/F (l/h) was as follows: