Population Pharmacokinetics of Tacrolimus in Adult Kidney Transplant Patients

Abstract

Objectives: The aims of this study were to develop a population pharmacokinetic model of tacrolimus in adult kidney transplant recipients; to use this model to compare cytochrome P450 3A5 (CYP3A5) genotype based initial dosing of tacrolimus to standard per-kilogram based dosing; and to predict the best starting dose of tacrolimus based on patient genotype to achieve a trough concentration between 6 and10 µg/L by day 5 post-transplantation.Methods: Population analysis was performed using the software program NONMEM®. Tacrolimus

Improved Tacrolimus Target Concentration Achievement Using Computerized Dosing in Renal Transplant Recipients—A Prospective, Randomized Study

“…The dose at discharge was 65% higher in CYP3A5 *1/*3 expressers (no *1/*1 expressers present), which is similar to previous observations (14,40). Yet, after the first measured concentration, the proportion of concentrations below the target range and time to reach the target was not different between CYP3A5 expressers and non-expressers for neither of the groups.…”

“…However, due to frequent dose adjustments Tac concentrations are typically not measured at steady state in the early phase after transplantation, and this complicates the intuitive dose adaptation approach. Furthermore, Tac dosing is challenged by its time-varying pharmacokinetics in the early phase after transplantation, which is partly due to systematic changes in hematocrit (12-14) and prednisolone dose (15-17). In previous studies, less than 60% of the Tac concentrations were within the target range in the early post-transplant phase using this approach (13,18,19).…”

Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in Chinese liver transplant patients

“…Clearance of TAC varied at various stages post‐transplantation. POD is considered as an important covariate in renal or liver transplant recipients . However, the effect is different among various studies.…”

“…MAP has the following advantages: patient characteristics can be incorporated into the model to improve the prediction of individualized AUC; the predictive performance can be improved with additional data; the sampling time can be chosen flexibly; and different PK parameters can be predicted simultaneously. Different TAC PPK models have been established in various populations including renal transplant patients, liver transplant patients, hematopoietic stem cell transplant patients and lung transplant patients . Some studies have tried to estimate TAC AUC using MAP.…”

Population pharmacokinetics of tacrolimus in paediatric systemic lupus erythematosus based on real-world study

“…[6][7][8][9][10][11][12][13][14][15] However, tacrolimus has a narrow therapeutic window and displays considerable interindividual and intra-individual variabilities in its pharmacokinetics, with poor correlation between drug dosage and blood concentrations, making it difficult to define an optimal dose schedule. 18 Currently, different tacrolimus PPK models have been set up for various populations including renal transplant patients, [19][20][21][22][23][24] liver transplant patients, [25][26][27][28][29][30] haematopoietic stem cell transplant patients 31 and lung transplant patients. Moreover, the population analysis methodology differentiates between interindividual variability and residual unexplained variability.…”