Tacrolimus dose requirement in pediatric liver transplantation: influence of CYP3A5 gene polymorphism.

ABSTRACT

AIM: Little information is available regarding the influence of CYP3A5 genetic polymorphisms on tacrolimus dose requirement in pediatric liver transplantation. PATIENTS & METHODS: We performed a retrospective study among 179 pediatric liver recipients grafted between 2002 and 2009 in order to determine the influence of donor CYP3A5 genotype along with clinical variables on tacrolimus daily dose requirement during the first weeks following transplantation. RESULTS: Mean stable tacrolimus daily dose requirement was higher among children who received a liver expressing CYP3A5 (carrying the CYPA3A5*1 allele) compared with those with a liver that did not express CYP3A5 (CYP3A5*3/*3 genotype) 0.29 ± 0.20 vs 0.18 ± 0.13 mg.kg(-1).d(-1), p = 0.005, respectively. A younger recipient age and fluconazole prescription were also significantly associated with tacrolimus daily dose requirement. Time to reach stable tacrolimus therapeutic trough concentrations was prolonged among patients with a CYP3A5-expressing graft (26 vs 21 days, p = 0.04). CONCLUSION: Donor CYP3A5 genotype partially explains tacrolimus dose requirement. Original submitted 30 January 2013; Revision submitted 2 May 2013.