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Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purposes

Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK of TAC in pediatric patients during the first year after transplantation.

Methods

Routine TDM trough levels of TAC were obtained from 42 pediatric liver allograft recipients during the first year after transplantation. A population PK model was developed using nonlinear mixed-effects modeling to describe TAC PK during this period and to explain the observed variability by means of patients’ demographics, biochemical test results and physiological characteristics.

Results

The PK of TAC were best described by a two-compartment model with first-order elimination. Apparent volumes of the central compartment, intercomparmental clearance and maximum blood clearance estimates were 253 L, 115 L/day and 314 L/day, respectively. The absorption first-order rate and volume of peripheral compartment were fixed to 4.5 h-1 and 100 L, respectively. While hematocrit levels, time after transplantation and bodyweight influenced TAC clearance, bodyweight was the only covariate retained on volume of distribution.

Conclusions

We developed a TAC population PK model in pediatrics covering the first year after liver transplantation that may serve as a tool for TAC dose individualization as part of TDM.

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Acknowledgments

We thank the pediatric coordinator Magda Janssens for patients’ data research support.

Conflict of interest statement

The authors declare no conflict of interest related to this work.

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Authors and Affiliations

  1. Louvain Center for Toxicology and Applied Pharmacology, Université catholique de Louvain, Brussels, Belgium

    V. Guy-Viterbo, A. Scohy, P. Wallemacq & Flora Tshinanu Musuamba

  2. Louvain Drug Research Institute, Université catholique de Louvain, Avenue Mounier 73, B. 7313, 1200, Brussels, Belgium

    R. K. Verbeeck & Flora Tshinanu Musuamba

  3. Transplantation Unit, St-Luc University Hospital, Université catholique de Louvain, Brussels, Belgium

    R. Reding

Authors
  1. V. Guy-Viterbo
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  2. A. Scohy
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  3. R. K. Verbeeck
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  4. R. Reding
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  5. P. Wallemacq
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  6. Flora Tshinanu Musuamba
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Corresponding author

Correspondence to Flora Tshinanu Musuamba.

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Guy-Viterbo, V., Scohy, A., Verbeeck, R.K. et al. Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation. Eur J Clin Pharmacol 69, 1533–1542 (2013). https://doi.org/10.1007/s00228-013-1501-0

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  • DOI: https://doi.org/10.1007/s00228-013-1501-0

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