title: Maturation of dose-corrected tacrolimus predose trough levels in pediatric kidney allograft recipients.
abstract: BACKGROUND
  In contrast to adult kidney recipients, in whom the long-term evolution and clinical determinants of tacrolimus pharmacokinetics are well studied, less is known about the long-term evolution of tacrolimus pharmacokinetics in pediatric kidney transplant recipients.
  
  
  METHODS
  One-hundred and five pediatric recipients of a kidney allograft, all treated with a corticosteroid-free immunosuppressive protocol, were included. The evolution of tacrolimus doses and predose trough (C0) levels was recorded at 3, 6, 9, 12, 18, and 24 months after transplantation, as well as all C0 levels obtained in the first 2 years after transplantation. The evolution and clinical determinants of tacrolimus exposure parameters were analyzed.
  
  
  RESULTS
  Dose-corrected tacrolimus C0 levels (C0/dose/kg) increased in the first 2 years after kidney transplantation in pediatric recipients (P=0.001). This decrease in dose requirement by time was only significant in children older than 5 years at the time of transplantation (P=0.38, 0.03, and 0.001 for age groups <5, 5-12, and >12 years, respectively). In addition, the younger patients had significantly higher dose requirements (dose/kg) compared with older recipients (P=0.0002).
  
  
  CONCLUSIONS
  Pediatric kidney transplant recipients exhibit maturation of dose-corrected tacrolimus predose trough levels with time after transplantation. This cannot be explained by differences in corticosteroid use, because all patients were treated with a corticosteroid-free protocol. The higher dose requirements for younger recipients and the absence of tacrolimus maturation in the youngest recipients suggest that age-dependent changes in tacrolimus intestinal first-pass effect, metabolism, or distribution play a role. Whether age-specific tacrolimus dosing algorithms will improve outcome needs further study.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA. maarten.naesens@uz.kuleuven.be
authors.forename: Maarten
authors.initials: M
authors.lastname: Naesens
authors.forename: Oscar
authors.initials: O
authors.lastname: Salvatierra
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Neeraja
authors.initials: N
authors.lastname: Kambham
authors.forename: Waldo
authors.initials: W
authors.lastname: Concepcion
authors.forename: Minnie
authors.initials: M
authors.lastname: Sarwal
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007223:Infant; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D008099:Liver / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D016559:Tacrolimus / Q000493:pharmacokinetics*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus