ArticleBritish journal of clinical pharmacology2014
Characterizing variability in warfarin dose requirements in children using modelling and simulation.
Article in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
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Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- CYP2C9, VKORC1, and CYP4F2 polymorphisms and pediatric warfarin maintenance dose: a systematic review and meta-analysis.The pharmacogenomics journal · 2020Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update.Clinical pharmacology and therapeutics · 2017Guideline
- AI-WAR: a novel warfarin management software with a bidirectional LSTM dosing model improves time in therapeutic range.Frontiers in pharmacology · 2026Article
- Protein C concentrate pharmacokinetics-no need to fear the curve.Research and practice in thrombosis and haemostasis · 2025Article
- A physiologically-based pharmacokinetic/pharmacodynamic modeling approach for drug-drug-gene interaction evaluation of S-warfarin with fluconazole.CPT: pharmacometrics & systems pharmacology · 2024Article
- New insights into the role of VKORC1 polymorphisms for optimal warfarin dose selection in Caribbean Hispanic patients through an external validation of a population PK/PD model.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Improved stacking ensemble learning based on feature selection to accurately predict warfarin dose.Frontiers in cardiovascular medicine · 2023Article
- Article
- Evaluation of the effects of ontogenetic or maturation functions and chronic heart failure on the model analysis for the dose-response relationship of warfarin in Japanese children.European journal of clinical pharmacology · 2019Article
- Height, VKORC1 1173, and CYP2C9 Genotypes Determine Warfarin Dose for Pediatric Patients with Kawasaki Disease in Southwest China.Pediatric cardiology · 2019Article
- Prediction of Warfarin Dose in Pediatric Patients: An Evaluation of the Predictive Performance of Several Models.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAGArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAlthough genetic, clinical and demographic factors have been shown to explain approximately half of the inter-individual variability in warfarin dose requirement in adults, less is known about causes of dose variability in children. This study aimed to identify and quantify major genetic, clinical and demographic sources of warfarin dose variability in children using modelling and simulation.
methodsClinical, demographic and genetic data from 163 children with a median age of 6.3 years (range 0.06-18.9 years), covering over 183 years of warfarin therapy and 6445 INR observations were used to update and optimize a published adult pharmacometric warfarin model for use in children.
resultsGenotype effects in children were found to be comparable with what has been reported for adults, with CYP2C9 explaining up to a four-fold difference in dose (CYP2C9 *1/*1 vs. *3/*3) and VKORC1 explaining up to a two-fold difference in dose (VKORC1 G/G vs. A/A), respectively. The relationship between bodyweight and warfarin dose was non-linear, with a three-fold difference in dose for a four-fold difference in bodyweight. In addition, age, baseline and target INR, and time since initiation of therapy, but not CYP4F2 genotype, had a significant impact on typical warfarin dose requirements in children.
conclusionsThe updated model provides quantitative estimates of major clinical, demographic and genetic factors impacting on warfarin dose variability in children. With this new knowledge more individualized dosing regimens can be developed and prospectively evaluated in the pursuit of improving both efficacy and safety of warfarin therapy in children.
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