ArticleThe journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG2013
Genetics-based pediatric warfarin dosage regimen derived using pharmacometric bridging.
Article in The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- CYP2C9, VKORC1, and CYP4F2 polymorphisms and pediatric warfarin maintenance dose: a systematic review and meta-analysis.The pharmacogenomics journal · 2020Pooled it
- Bayesian model-guided antimicrobial therapy in pediatrics.Frontiers in pharmacology · 2023Review
- A Systematic Review of Polygenic Models for Predicting Drug Outcomes.Journal of personalized medicine · 2022Review
- Height, VKORC1 1173, and CYP2C9 Genotypes Determine Warfarin Dose for Pediatric Patients with Kawasaki Disease in Southwest China.Pediatric cardiology · 2019Article
- Perceptions of students in health and molecular life sciences regarding pharmacogenomics and personalized medicine.Human genomics · 2018Article
- Pharmacogenomics in Pediatric Patients: Towards Personalized Medicine.Paediatric drugs · 2016Review
- Generating Virtual Patients by Multivariate and Discrete Re-Sampling Techniques.Pharmaceutical research · 2015Article
- Utility of a dedicated pediatric cardiac anticoagulation program: the Boston Children's Hospital experience.Pediatric cardiology · 2015Article
- Design and anticipated outcomes of the eMERGE-PGx project: a multicenter pilot for preemptive pharmacogenomics in electronic health record systems.Clinical pharmacology and therapeutics · 2014Article
- Review
- Ethical issues in pediatric pharmacogenomics.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2013Article
- 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 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWarfarin dosage regimens using CYP2C9 and VKORC1 polymorphisms have been extensively studied in adults and is included in US Food and Drug Administration-approved warfarin labeling. However, no dosage algorithm is available for pediatric patients.
objectiveTo derive a genetics-based pediatric dosge regimen for warfarin, including starting dose and titration scheme.
methodsA model-based approach was developed based on a previously validated warfarin dosage model in adults, with subsequent comparison to pediatric data from pediatric warfarin dose, genotyping, and international normalized ratio (INR) results. The adult model was based on a previously established model from the CROWN (CReating an Optimal Warfarin dosing Nomogram) trial. Pediatric warfarin data were obtained from a study conducted at the Children's Hospital of Los Angeles with 26 subjects. Variant alleles of CYP2C9 (rs1799853 or *2, and rs1057910 or *3) and the VKORC1 single nucleotide polymorphism (SNP) rs9923231 (-1639 G>A) were assessed, where the rs numbers are reference SNP identification tags assigned by the National Center for Biotechnology Information.
resultsA pediatric warfarin model was derived using the previously validated model and clinical pharmacology considerations. The model was validated, and clinical trial simulation and stochastic modeling were used to optimize pediatric dosage and titration. The final dosage regimen was optimized based on simulations targeting a high (≥60%) proportion of INRs within the therapeutic range by week 2 of warfarin therapy while minimizing INRs >3.5 or <2.
conclusionsThe proposed pediatric warfarin dosage scheme based on individual CYP2C9 (alleles *1,*2,*3) and VKORC1 rs9923231 (-1639 G>A) genotypes may offer improved dosage compared to current treatment strategies, especially in patients with variant CYP2C9 and VKORC1 alleles. This pilot study provides the foundation for a larger prospective evaluation of genetics-based warfarin dosage in pediatric patients.
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