Population pharmacokinetics and pharmacogenetics of tacrolimus in de novo pediatric kidney transplant recipients.
Clin Pharmacol Ther
; 86(6): 609-18, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19865079
ABSTRACT
The aim of this study was to develop a population pharmacokinetic model of tacrolimus in pediatric kidney transplant patients, identify factors that explain variability, and determine dosage regimens. Pharmacokinetic samples were collected from 50 de novo pediatric kidney transplant patients (age 2-18 years) who were on tacrolimus treatment. Population pharmacokinetic analysis of tacrolimus was performed using NONMEM, and the impact of variables (demographic and clinical factors, and CYP3A4-A5, ABCB1, and ABCC2 polymorphisms) was tested. The pharmacokinetic data were described by a two-compartment model that incorporated first-order absorption and lag time. The apparent oral clearance (CL/F) was significantly related to body weight (allometric scaling); in addition, it was higher in patients with low hematocrit levels and lower in patients with CYP3A5*3/*3. The population pharmacokinetic-pharmacogenetic model developed in de novo pediatric kidney transplant patients demonstrated that, in children, tacrolimus dosage should be based on weight, hematocrit levels, and CYP3A5 polymorphism. Individualization of therapy will enable the optimization of tacrolimus exposure, with resultant beneficial effects on kidney function in the initial post-transplantation period.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adolescent
/
Child
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Child, preschool
/
Female
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article