Predicting the relative importance of genetic, clinical and demographic factors on warfarin dose in children using pharmacometric modelling
(English)Article in journal (Other academic) Submitted
It is difficult to predict anticoagulation response to warfarin in children mainly because of a wide inter-individual variability in warfarin dose requirement. The present study objective was to identify important predictors of dose in children and to optimize a previous NONMEM warfarin model for a priori and a posteriori dose and INR predictions in children. Data from 163 warfarin treated children with underlying heart disease (median age 6.3 years) were used. CYP2C9 and VKORC1 genotype caused up to 4-fold and 2-fold differences in warfarin dose requirement, respectively. Other important predictors of warfarin dose were bodyweight, age, baseline and target INR, and time since initiation of therapy with lower doses during the initiation. CYP4F2 genotype had only a marginal effect on dose. The present study findings will aid the development of a personalised approach to warfarin therapy in children, in the pursuit of improving both efficacy and safety of anticoagulation therapy.
Pharmacometric model, warfarin, dose individualisation, children
Research subject Cardiology; Pharmaceutical Pharmacology
IdentifiersURN: urn:nbn:se:uu:diva-197597OAI: oai:DiVA.org:uu-197597DiVA: diva2:613633
FunderSwedish Heart Lung Foundation