Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation.
Eur J Clin Pharmacol
; 69(8): 1533-42, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23588560
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Transplante de Fígado
/
Tacrolimo
/
Imunossupressores
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Child
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Child, preschool
/
Female
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Humans
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Infant
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Bélgica