6533b861fe1ef96bd12c57eb

RESEARCH PRODUCT

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

Claudia Rosso FelipeFabiana Dalla Vecchia GenvigirRosario Dominguez Crespo HirataJose O. Medina-pestanaAlvaro CerdaMaría José HerreroAntony Brayan Campos-salazarAntony Brayan Campos-salazarMario Hiroyuki HirataSalvador F. AliñoHelio Tedesco-silvaSonia De Quateli Doi

subject

PharmacologyKidneymedicine.medical_specialtyEverolimusbiologybusiness.industryGastroenterologyTacrolimusMycophenolic acidmedicine.anatomical_structurePharmacokineticsInternal medicineGeneticsmedicinebiology.proteinFARMACOCINÉTICAMolecular MedicineSLCO1B1CYP3A5businessCYP2C8medicine.drug

description

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.

yearjournalcountryeditionlanguage
2020-01-01
10.2217/pgs-2019-0120