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

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.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Genvigir FDV,Campos-Salazar AB,Felipe CR,Tedesco-Silva H Jr,Medina-Pestana JO,Doi SQ,Cerda A,Hirata MH,Herrero MJ,Aliño SF,Hirata RDC

doi

10.2217/pgs-2019-0120

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

7-21

issue

1

eissn

1462-2416

issn

1744-8042

journal_volume

21

pub_type

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