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Guy-Viterbo V.,Cliniques Universitaires Saint | Guy-Viterbo V.,Cliniques Universitaires Saint Luc | Baudet H.,Groupe Medico Chirurgical dHepatologie Pediatrique | Elens L.,Cliniques Universitaires Saint | And 8 more authors.
Pharmacogenomics | Year: 2014

Aim: To characterize the effect of donor and recipient CYP3A4, CYP3A5 and ABCB1 genotypes as well as relevant patient characteristics on tacrolimus pharmacokinetics in pediatric liver transplantation. Patients & methods: Data from 114 pediatric liver transplant recipients were retrospectively collected during the first 3 months following transplantation. Population pharmacokinetic analysis was performed using nonlinear mixed effects modeling, including characterization of influential covariates. Results: A two-compartment model with first order elimination best fitted the data. Estimates of apparent volume of the central compartment, intestinal clearance, hepatic clearance and intercompartmental clearance were 79 l, 0.01 l/h, 10.9 l/h and 105 l/h, respectively. Time post-transplantation, recipient age, donor CYP3A5 and CYP3A4 genotypes and fluconazole administration significantly influenced tacrolimus apparent clearance while bodyweight influenced volume of distribution. Conclusion: The proposed model displayed acceptable fitting performances and enabled identification of statistically significant and clinically relevant covariates on tacrolimus pharmacokinetics in the early pediatric post liver transplantation period. © 2014 Future Medicine Ltd.

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