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Eur J Clin Pharmacol. 2013 Aug;69(8):1533-42. doi: 10.1007/s00228-013-1501-0. Epub 2013 Apr 16.

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

Author information

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

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.

PMID:
23588560
DOI:
10.1007/s00228-013-1501-0
[Indexed for MEDLINE]

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