Background And Objectives: Tacrolimus(PR) is a new prolonged-release once-daily formulation of the calcineurin inhibitor tacrolimus, currently used in adult transplant patients. As there are no pharmacokinetic data available in pediatric kidney transplant recipients, the aims of this study were to develop a population pharmacokinetic model of tacrolimus(PR) in pediatric and adolescent kidney transplant recipients and to identify covariates that have a significant impacts on tacrolimus(PR) pharmacokinetics, including CYP3A5 polymorphism.
Methods: Pharmacokinetic samples were collected from 22 pediatric kidney transplant patients. Population pharmacokinetic analysis was performed using NONMEM. Pharmacogenetic analysis was performed on the CYP3A5 gene.
Results: The pharmacokinetic data were best described by a one-compartment model with first order absorption and lag-time. The weight normalized oral clearance CL/F [CL/F/ (weight/70)(0.75)] was lower in patients with CYP3A5 3/3 as compared to patients with the CYP3A5 1/3 (32.2 ± 10.1 vs. 53.5 ± 20.2 L/h, p = 0.01).
Conclusions: The population pharmacokinetic model of tacrolimus(PR) was developed and validated in pediatric and adolescent kidney transplant patients. Body weight and CYP3A5 polymorphism were identified as significant factors influencing pharmacokinetics. The developed model could be useful to optimize individual pediatric tacrolimus (PR) dosing regimen in routine clinical practice.
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