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Warfarin dose prediction in children using pharmacometric bridging--comparison with published pharmacogenetic dosing
Anna-Karin Hamberg1, Lena E Friberg, Katarina Hanséus
1Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Entrance 61 3rd floor, SE-751 85, Uppsala, Sweden. anna-karin.hamberg@medsci.uu.se
European Journal of Clinical Pharmacology
|January 12, 2013
Summary
A bridged adult warfarin model shows promise for pediatric dosing, improving prediction accuracy with dose optimization. Further research is needed for precise warfarin dosing in children.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Pharmacometrics
Background:
- Warfarin dosing variability is well-studied in adults but less so in children.
- Population modeling can transfer knowledge between populations.
- Limited data exists on pediatric warfarin dosing algorithms.
Purpose of the Study:
- Evaluate an adult warfarin model's predictive performance in children.
- Compare this bridged model's accuracy to existing pediatric warfarin algorithms.
- Assess the potential for individualized pediatric warfarin therapy.
Main Methods:
- Bridged an adult population pharmacokinetic/pharmacodynamic (PK/PD) model to children using allometric scaling.
- Included CYP2C9 and VKORC1 genotype, age, and target INR as predictors.
- Validated the model on an external dataset of children (0-18 years) and compared it with published algorithms.
Main Results:
- The bridged model predicted INR response well in 64 children, with overprediction in those ≤2 years old.
- It predicted 41% of children within ±20% of the actual maintenance dose.
- Dose optimization using the bridged model improved prediction accuracy to 70% within ±20%.
Conclusions:
- A mechanism-based population model from adult data is a viable starting point for pediatric warfarin therapy.
- This approach offers potential for more individualized warfarin dosing in children.
- Further refinement may enhance accuracy across all pediatric age groups.
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