PURPOSES: 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.
PURPOSES: 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: M Yasuhara; T Hashida; M Toraguchi; Y Hashimoto; M Kimura; K Inui; R Hori; Y Inomata; K Tanaka; Y Yamaoka Journal: Transplant Proc Date: 1995-02 Impact factor: 1.066
Authors: Pierre Wallemacq; Jean-Sebastien Goffinet; Susan O'Morchoe; Thomas Rosiere; Gregory T Maine; Myriam Labalette; Giuseppe Aimo; Diana Dickson; Ed Schmidt; Reinhard Schwinzer; Rainer W Schmid Journal: Ther Drug Monit Date: 2009-04 Impact factor: 3.681
Authors: Agnieszka A Prytuła; Karlien Cransberg; Antonia H M Bouts; Ron H N van Schaik; Huib de Jong; Saskia N de Wildt; Ron A A Mathôt Journal: Clin Pharmacokinet Date: 2016-09 Impact factor: 6.447
Authors: Shwetal Lalan; Susan Abdel-Rahman; Andrea Gaedigk; J Steven Leeder; Bradley A Warady; Hongying Dai; Douglas Blowey Journal: Pediatr Nephrol Date: 2014-05-30 Impact factor: 3.714