Impact of the CYP3A5 genotype on the distributions of dose-adjusted trough concentrations and incidence of rejection in Japanese renal transplant recipients receiving different tacrolimus formulations.
Clin Exp Nephrol
; 21(5): 787-796, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28271256
ABSTRACT
BACKGROUND:
We investigated the impact of the CYP3A5 genotype on the distributions of dose-adjusted trough concentrations (C 0h/D) and the incidence of rejection in Japanese recipients taking twice-daily (Tac-BID, n = 140) or modified-release once-daily (Tac-QD, n = 80) tacrolimus formulations for 1 year after renal transplantation.METHODS:
Logistic regression analysis was carried out to estimate the distinction rate of CYP3A5 genotypes based on the C 0h/D of Tac-BID or Tac-QD. The coefficients of variation (%CVs) were compared in each recipient to estimate the stability of tacrolimus C 0h/D between formulations or CYP3A5 genotypes.RESULTS:
Recipients with at least one CYP3A5*1 wild-type allele (EMs) and recipients with homozygous expression of the variant allele CYP3A5*3 (PMs) were significantly identified using the tacrolimus C 0h/D cut-off values of 2.77 and 0.85 ng/mL/mg, respectively, and discrimination rates of 75.3 and 85.4%, respectively, for Tac-BID and Tac-QD groups. The %CV of the tacrolimus C 0h/D in CYP3A5 EMs taking Tac-QD was significantly lower than that in those taking Tac-BID (20.4 versus 23.3%, P = 0.003). The %CV of the tacrolimus C 0h/D was an independent risk factor for rejection (odds ratio = 1.028, P = 0.033).CONCLUSIONS:
The tacrolimus C 0h/D values with definite cut-offs for CYP3A5 genotypes were specifically identified in Japanese renal transplant recipients taking Tac-QD. In addition, a larger %CV for the tacrolimus C 0h/D correlated with the incidence of rejection. Consequently, the stability of the C 0h/D achieved using Tac-QD, which was clearly influenced by the CYP3A5 polymorphism, may prevent the development of rejection.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
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Tacrolimo
/
Citocromo P-450 CYP3A
/
Inibidores de Calcineurina
/
Variantes Farmacogenômicos
/
Rejeição de Enxerto
/
Imunossupressores
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Clin Exp Nephrol
Ano de publicação:
2017
Tipo de documento:
Article