Population pharmacokinetic analysis of tacrolimus in Mexican paediatric renal transplant patients: role of CYP3A5 genotype and formulation.
Br J Clin Pharmacol
; 80(4): 630-41, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-25846845
ABSTRACT
AIMS:
The aims of this study were (i) to develop a population pharmacokinetic (PK) model of tacrolimus in a Mexican renal transplant paediatric population (n = 53) and (ii) to test the influence of different covariates on its PK properties to facilitate dose individualization.METHODS:
Population PK and variability parameters were estimated from whole blood drug concentration profiles obtained at steady-state using the non-linear mixed effect modelling software NONMEM® Version 7.2.RESULTS:
Tacrolimus PK profiles exhibited high inter-patient variability (IPV). A two compartment model with first order input and elimination described the tacrolimus PK profiles in the studied population. The relationship between CYP3A5 genotype and tacrolimus CL/F was included in the final model. CL/F in CYP3A5*1/*1 and *1/*3 carriers was approximately 2- and 1.5-fold higher than in CYP3A5*3/*3 carriers (non-expressers), respectively, and explained almost the entire IPV in CL/F. Other covariates retained in the final model were the tacrolimus dose and formulation type. Limustin® showed markedly lower concentrations than the rest of the formulations.CONCLUSIONS:
Population PK modelling of tacrolimus in paediatric renal transplant recipients identified the tacrolimus formulation type as a significant covariate affecting the blood concentrations and confirmed the previously reported significant effect of CYP3A5 genotype on CL/F. It allowed the design of a proposed dosage based on the final model that is expected to help to improve tacrolimus dosing.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
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Tacrolimo
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Citocromo P-450 CYP3A
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Imunossupressores
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
País como assunto:
Mexico
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article