CYP3A5*3 and CYP2C8*3 variants influence exposure and clinical outcomes of tacrolimus-based therapy

Genvigir, FD; Campos-Salazar, AB; Felipe, CR; Tedesco-Silva, H; Medina-Pestana, JO; Doi, SD; Cerda, A; Hirata, MH; Herrero, MJ; Alino, SF; Hirata, RDC

Keywords: pharmacokinetics, pharmacogenomics, tacrolimus, mycophenolic acid, kidney transplant, everolimus

Abstract

Aim: The influence of variants in pharmacokinetics-related genes on long-term exposure to tacrolimus (TAC)-based therapy and clinical outcomes was investigated. Patients & methods: Brazilian kidney recipients were treated with TAC combined with everolimus (n = 178) or mycophenolate sodium (n = 97). The variants in CYP2C8, CYP2J2, CYP3A4, CYP3A5, POR, ABCB1, ABCC2, ABCG2, SLCO1B1 and SLCO2B1 were analyzed. Main results:CYP3A5*3/*3 genotype influenced increase in TAC concentration from week 1 to month 6 post-transplantation (p < 0.05). The living donor and CYP2C8*3 variant were associated with reduced risk for delayed graft function (OR = 0.07; 95% CI = 0.03-0.18 and OR = 0.45; 95% CI = 0.20-0.99, respectively, p < 0.05). Conclusion: The CYP3A5*3 variant is associated with increased early exposure to TAC. Living donor and CYP2C8*3 variant seem to be protective factors for delayed graft function in kidney recipients.

Más información

Título según WOS: CYP3A5*3 and CYP2C8*3 variants influence exposure and clinical outcomes of tacrolimus-based therapy
Título de la Revista: PHARMACOGENOMICS
Volumen: 21
Número: 1
Editorial: Future Medicine Ltd.
Fecha de publicación: 2020
Página de inicio: 7
Página final: 21
Idioma: English
DOI:

10.2217/pgs-2019-0120

Notas: ISI