title: Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation.
abstract: OBJECTIVE
  Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK of TAC in pediatric patients during the first year after transplantation.
  
  
  METHODS
  Routine TDM trough levels of TAC were obtained from 42 pediatric liver allograft recipients during the first year after transplantation. A population PK model was developed using nonlinear mixed-effects modeling to describe TAC PK during this period and to explain the observed variability by means of patients' demographics, biochemical test results and physiological characteristics.
  
  
  RESULTS
  The PK of TAC were best described by a two-compartment model with first-order elimination. Apparent volumes of the central compartment, intercomparmental clearance and maximum blood clearance estimates were 253 L, 115 L/day and 314 L/day, respectively. The absorption first-order rate and volume of peripheral compartment were fixed to 4.5 h(-1) and 100 L, respectively. While hematocrit levels, time after transplantation and bodyweight influenced TAC clearance, bodyweight was the only covariate retained on volume of distribution.
  
  
  CONCLUSIONS
  We developed a TAC population PK model in pediatrics covering the first year after liver transplantation that may serve as a tool for TAC dose individualization as part of TDM.
authors.affiliation: Louvain Center for Toxicology and Applied Pharmacology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Guy-Viterbo
authors.forename: A
authors.initials: A
authors.lastname: Scohy
authors.forename: R K
authors.initials: RK
authors.lastname: Verbeeck
authors.forename: R
authors.initials: R
authors.lastname: Reding
authors.forename: P
authors.initials: P
authors.lastname: Wallemacq
authors.forename: Flora Tshinanu
authors.initials: FT
authors.lastname: Musuamba
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007223:Infant; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016559:Tacrolimus / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus