Population Pharmacokinetic Analysis of Tacrolimus in Adult Mexican Patients with Renal Transplant

The aim of this study was to estimate the population pharmacokinetic parameters of Tacrolimus in Mexican adults undergoing kidney transplantation and to identify the clinical factors affecting Tacrolimus pharmacokinetics. Using Non-linear mixed effects modeling (NONMEM) with First-order absorption and elimination, a total of 592 retrospective-prospective drug monitoring data points were collected from 36 patients with renal transplant receiving Tacrolimus (Prograf® twice daily during the first 6 post-transplantation months and a generic product thereafter. The absorption rate constant was fixed at 4.5 h–1, and the following population pharmacokinetic estimates were obtained: Tacrolimus clearance (CL/F), 22.5 L/h, and apparent volume of distribution (V/F), 812 L. Interindividual variability was 52.9 and 82.1% for CL/F and V/F, respectively. The covariates that significantly affect Tacrolimus pharmacokinetics parameters were concomitantly administered calcium channel blocker drug and hematocrit level. The population pharmacokinetic analysis identified important sources of variability in Tacrolimus pharmacokinetics. The model will help to calculate Tacrolimus dose requirements in Mexican renal transplant recipients according to specific clinical factors affecting Tacrolimus clearance and volume of distribution and it will also be useful for therapeutic drug monitoring.