title: Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a pharmacokinetic and bioequivalence study.
abstract: BACKGROUND
  The objectives of this study were to investigate pharmacokinetic and pharmacogenetic parameters during the conversion on a 1:1 (mg:mg) basis from a twice-daily (Prograf) to once-daily (Advagraf) tacrolimus formulation in pediatric kidney transplant recipients.
  
  
  METHODS
  Twenty-four-hour pharmacokinetic profiles were analyzed before and after conversion in 19 stable renal transplant recipients (age 7-19 years). Tacrolimus pharmacokinetic parameters [area under the concentration-time curve (AUC0-24), minimum whole-blood concentration (Cmin), maximum whole-blood concentration (Cmax), and time to achieve maximum whole-blood concentration (tmax)] were compared between Tac formulations and between CYP3A5 and MDR1 genotypes after dose normalization.
  
  
  RESULTS
  Both AUC0-24 and Cmin decreased after conversion (223.3 to 197.5 ng.h/ml and 6.5 to 5.6 ng/ml; p = 0.03 and 0.01, respectively). However, the ratio of the least square means (LSM) for AUC0-24 was 90.8 %, with 90 % CI limits of 85.3 to 96.7 %, falling within bioequivalence limits. The CYP3A5 genotype influences the dose-normalized Cmin with the twice-daily formulation only.
  
  
  CONCLUSIONS
  Both tacrolimus formulations are bioequivalent in pediatric renal recipients. However, we observed a decrease in AUC0-24 and Cmin after the conversion, requiring close pharmacokinetic monitoring during the conversion period.
authors.affiliation: Service de Néphrologie, Département de Pédiatrie, CHU de Sainte-Justine, Université de Montréal, Montréal, Canada, anne.laure.lapeyraque@umontreal.ca.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Lapeyraque
authors.forename: Nastya
authors.initials: N
authors.lastname: Kassir
authors.forename: Yves
authors.initials: Y
authors.lastname: Théorêt
authors.forename: Maja
authors.initials: M
authors.lastname: Krajinovic
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Clermont
authors.forename: Catherine
authors.initials: C
authors.lastname: Litalien
authors.forename: Véronique
authors.initials: V
authors.lastname: Phan
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D010597:Pharmacogenetics; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus