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