title: Tacrolimus dose requirement in pediatric liver transplantation: influence of CYP3A5 gene polymorphism.
abstract: OBJECTIVE
  Little information is available regarding the influence of CYP3A5 genetic polymorphisms on tacrolimus dose requirement in pediatric liver transplantation.
  
  
  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).
  
  
  CONCLUSIONS
  Donor CYP3A5 genotype partially explains tacrolimus dose requirement. Original submitted 30 January 2013; Revision submitted 2 May 2013.
authors.affiliation: Pediatric Intensive Care Department, Assistance Publique Hôpitaux de Paris, Bicêtre Hospital, le Kremlin Bicêtre, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Durand
authors.forename: Dominique
authors.initials: D
authors.lastname: Debray
authors.forename: Mikaela
authors.initials: M
authors.lastname: Kolaci
authors.forename: Jerome
authors.initials: J
authors.lastname: Bouligand
authors.forename: Valérie
authors.initials: V
authors.lastname: Furlan
authors.forename: Monique
authors.initials: M
authors.lastname: Fabre
authors.forename: Alexia
authors.initials: A
authors.lastname: Letierce
authors.forename: Céline
authors.initials: C
authors.lastname: Verstuyft
authors.forename: Laurent
authors.initials: L
authors.lastname: Becquemont
mesh_terms: D000483:Alleles; D002648:Child; D002675:Child, Preschool; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation; D008297:Male; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus