title: Limited sampling strategy using Bayesian estimation for estimating individual exposure of the once-daily prolonged-release formulation of tacrolimus in kidney transplant children.
abstract: BACKGROUND
  A limited sampling strategy (LSS) for estimating the area under the curve (AUC) of the prolonged-release formulation of tacrolimus (tacrolimus(PR)) is not available in pediatric patients, although the method is of real benefit to children. The objective of this study was to develop and validate a reliable and clinically applicable LSS using Bayesian estimation for estimating tacrolimus(PR) AUC in pediatric kidney transplant patients
  
  
  METHODS
  The original tacrolimus pharmacokinetic dataset consisted of 22 full profiles from 22 pediatric kidney transplant patients. The Bayesian estimation method was used to develop the LSS. External validation was performed in an independent validation group which consisted of 20 full pharmacokinetic profiles from 12 pediatric kidney transplant patients.
  
  
  RESULTS
  Bayesian estimator using C0h C2h and C3h gave the best predictive performance with a mean prediction error of 2.2 % in the external validation dataset. There was no correlation between the prediction error and age. The Bland-Altman analysis showed that the mean difference between the reference and Bayesian-estimated AUC0-24 was 3.5 (95 % confidence interval -3.5-10.5) ng h/mL CONCLUSIONS: A reliable and clinically applicable LSS for estimating AUC0-24 of tacrolimus(PR) was determined and validated in children. The prediction was unbiased and precise. It can be used as a routine procedure to perform AUC-based tacrolimus(PR) dosage optimization in pediatric renal transplant patients.
authors.affiliation: Department of Pediatric Pharmacology and Pharmacogenetics, Assistance Publique Hôpitaux de Paris (AP-HP), INSERM Clinical Investigation Center CIC9202-Hôpital Robert Debré, 48 Boulevard Sérurier, 75935 Paris Cedex 19, France. wei.zhao@rdb.aphp.fr
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Anne
authors.initials: A
authors.lastname: Maisin
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudouin
authors.forename: May
authors.initials: M
authors.lastname: Fakhoury
authors.forename: Thomas
authors.initials: T
authors.lastname: Storme
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jacqz-Aigrain
mesh_terms: D000293:Adolescent; D001499:Bayes Theorem; D001800:Blood Specimen Collection / Q000706:statistics & numerical data*; D002675:Child, Preschool; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D006801:Humans; D016030:Kidney Transplantation; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus