Influence of Combined CYP3A4 and CYP3A5 Single-Nucleotide Polymorphisms on Tacrolimus Exposure in Kidney Transplant Recipients: A Study According to the Post-Transplant Phase

• DOI: 10.2217/pgs.15.138
• Publication Date: 2015-11-30T12:06:07Z
• Authors: Karim Aouam; Abdessalem Kolsi; Emna Kerkeni; Nadia Ben Fredj; Amel Chaabane; Kamel Monastiri; Naceur Boughattas
• Keywords: CYP3A; Therapeutic index

The present study investigated in Tunisian renal transplant patients, genetic polymorphisms of CYP3A4 -392A>G and CYP3A5 6986A>G their influence on tacrolimus (Tac) pharmacokinetics during early late post-transplant (PT) phases established customized ranges Tac doses matching the C0 target levels according to genotype combination PT phase.We included adult patients having received for de novo kidney grafts undergone a therapeutic drug monitoring by morning (1 90 days) (over phases. genomic DNA was extracted from peripheral blood mononuclear cells using salting-out procedure. promoter (rs2740574; -392A>G) (rs776746; 6986A>G) SNP genotyping analyzed PCR-RFLP.Fifty-two were enrolled study. During phase, polymorphism but not that CYP3A4, correlates significantly with dose-normalized (C0/D ratio). effect becomes significant nonsignificant C0/D Tac. mean daily (mg/kg) C0, regardless CYP3A genotypes, 0.16 ± 0.05 0.10 respectively. Carriers CYP3A4*1B allele require higher maintain range two However, carrying CYP3A5*1 doses, only phase.Our data support critical role variation exposure establishment CYP3A4/CYP3A5 time, may allow preventing graft rejection improving safety profile this drug. Further studies are needed investigate issue.