title: Donor CYP3A5 genotype influences tacrolimus disposition on the first day after paediatric liver transplantation.
abstract: The aim of the present study was to investigate the influence of the cytochrome P450 (CYP) 3A4/5 genotype in paediatric liver transplant recipients and donors, and the contribution of age and gender to tacrolimus disposition on the first day after transplantation.
  
  
  
  The contribution of the CYP3A4/5 genotype in paediatric liver transplant recipients and donors to the tacrolimus blood trough concentrations (C0) and the tacrolimus concentration/weight-adjusted dose ratio on day 1 was evaluated in 67 liver-transplanted children: 33 boys and 34 girls, mean age 4.5 years.
  
  
  
  Donor CYP3A5 genotype appears to be significantly associated with tacrolimus disposition on the first day after liver transplantation (P < 0.0002). Other physiological factors, such as recipient age and donor gender may also play a role and lead to significant differences in tacrolimus C0and tacrolimus concentration/weight-adjusted dose ratio on day 1. However, according to the general linear model, only recipient age appears to be independently associated with tacrolimus disposition on the first day after liver transplantation (P < 0.03). Indeed, there was a faster tacrolimus metabolism in children under 6 years of age (P < 0.02).
  
  
  
  Donor CYP3A5 genotype, recipient age and, to a lesser extent, donor gender appear to be associated with tacrolimus disposition on day 1 after transplant. This suggests that increasing the starting tacrolimus doses in paediatric patients under 6 years of age who receive a graft from a male extensive metabolizer may enhance the possibility of their tacrolimus levels reaching the therapeutic range sooner.
authors.affiliation: Department of Pediatrics and Public Health Sciences, Division of Pediatric Gastroenterology, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Calvo
authors.affiliation: Department of Drug Science and Technology, University of Torino, Torino, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Serpe
authors.affiliation: Department of Surgical Sciences, Liver Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brunati
authors.affiliation: Clinical Biochemistry Unit, A.O.U. Città della Salute e della Scienza of Torino, Torino, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Nonnato
authors.affiliation: Department of Medical Sciences, Regional Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bongioanni
authors.affiliation: Department of Medical Sciences, Regional Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Dominic Dell'
authors.initials: DD
authors.lastname: Olio
authors.affiliation: Department of Pediatrics and Public Health Sciences, Division of Pediatric Gastroenterology, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Pinon
authors.affiliation: Department of Drug Science and Technology, University of Torino, Torino, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferretti
authors.affiliation: Department of Surgical Sciences, Liver Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tandoi
authors.affiliation: Department of Surgical Sciences, Liver Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Carbonaro
authors.affiliation: Department of Surgical Sciences, Liver Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Salizzoni
authors.affiliation: Department of Medical Sciences, Regional Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.affiliation: Department of Surgical Sciences, Liver Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Romagnoli
authors.affiliation: Department of Drug Science and Technology, University of Torino, Torino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Canaparo
mesh_terms: D000293:Adolescent; D000375:Aging; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007223:Infant; D016014:Linear Models; D016031:Liver Transplantation; D008297:Male; D012727:Sex Characteristics; D016559:Tacrolimus / Q000493:pharmacokinetics*; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
keywords: CYP3A genotyping; children; immunosuppression; liver transplantation; tacrolimus; therapeutic drug monitoring