Influence of donor-recipient CYP3A4/5 genotypes, age and fluconazole on tacrolimus pharmacokinetics in pediatric liver transplantation: a population approach
(2014) Pharmacogenomics — Vol. 15, n° 9, p. 1207-1221 (2014)
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- 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.
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Guy-Viterbo, V., Baudet, H., Elens, L., Haufroid, V., Lacaille, F., Girard, M., Debray, D., Chardot, C., Reding, R., Wallemacq, P., & Musuamba, F. (2014). Influence of donor-recipient CYP3A4/5 genotypes, age and fluconazole on tacrolimus pharmacokinetics in pediatric liver transplantation: a population approach. Pharmacogenomics, 15(9), 1207-1221. https://doi.org/10.2217/pgs.14.75 (Original work published 2014)