ESPN 51th Annual Meeting

ESPN 2018


 
Extrapolation of an adult computer-dosing tool for tacrolimus to organ transplanted children
ANNA BJERRE 1 MARTE T GUSTAVSEN 2 ELISABET STORSET 2 RUNAR ALMAAS 3 ANDERS ASBERG 2

1- DIVISION OF PAEDIATRIC AND ADOLSECENT MEDICINE
2- DEPARTMENT OF TRANSPLANTATION MEDICINE
3- DEPARTMENT OF PEDITARIC RESEARCH
 
Introduction:

Tacrolimus is the cornerstone immunosuppressive drug in many transplant centers. Therapeutic drug monitoring (TDM) is mandatory but challenging due to large pharmacokinetic variability, especially in pediatric patients. We have previously shown significantly more accurate dosing in adult renal transplants using a computer tool based on population pharmacokinetics. Using this kind of computer tools and 2-3 samples within a dose interval it is possible to apply the gold standard area under the curve (AUC) guided dosing instead of suboptimal C0 monitoring. The aim of the present study was to extrapolate this tool to children.

Material and methods:

The adult population model was developed with the non-parametric adaptive grid method integrated in Pmetrics for R. The model was allometrically scaled by fat-free mass and included the following covariates; hematocrit, days after transplantation and CYP3A5 genotype. Predictive error was assessed in 1386 tacrolimus concentrations from 64 transplanted children (44 kidney 20 liver age 1-18 years) using the full model as well as models without covariates and body size scaling.

Results:

The body size scaled model significantly over predicted tacrolimus concentrations while the model without body size scaling showed good predictions in children above 8 to 10 years of age. Below this age all models significantly under-predicted tacrolimus concentrations.

Conclusions:

Children from 8 to 10 years of age display similar absolute pharmacokinetic properties as adults and can be dosed using the same computer tool without correction by weight. For younger children specific models probably need to be developed.