ArticleClinical chemistry2009
Interactive modeling for ongoing utility of pharmacogenetic diagnostic testing: application for warfarin therapy.
Article in Clinical chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Pharmacogenetics-Based versus Conventional Dosing of Warfarin: A Meta-Analysis of Randomized Controlled Trials.PloS one · 2015Pooled it
- Trial
- Genetics informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT): rationale and study design.The pharmacogenomics journal · 2012Trial
- Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation.Thrombosis and haemostasis · 2012Trial
- Evaluation of methods for achieving stable INR in healthy subjects during a multiple-dose warfarin study.European journal of clinical pharmacology · 2012Trial
- Ethnic Diversity and Warfarin Pharmacogenomics.Frontiers in pharmacology · 2022Review
- Genetic risk assessment towards warfarin application: Saudi Arabia study with a potential to predict and prevent side effects.Saudi journal of biological sciences · 2020Article
- Effects of CYP2C9 and VKORC1 polymorphisms on warfarin sensitivity and responsiveness during the stabilization phase of therapy.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2019Article
- Impact ofGenes · 2018Article
- How to use warfarin assays in patient management: analysis of 437 warfarin measurements in a clinical setting.Clinical pharmacokinetics · 2015Article
- Review
- Prediction of warfarin maintenance dose in Han Chinese patients using a mechanistic model based on genetic and non-genetic factors.Clinical pharmacokinetics · 2013Article
- Effect of genetic variants, especially CYP2C9 and VKORC1, on the pharmacology of warfarin.Seminars in thrombosis and hemostasis · 2012Review
- Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy.Thrombosis and haemostasis · 2012Article
- Canalization effect in the coagulation cascade and the interindividual variability of oral anticoagulant response. A simulation study.Theoretical biology & medical modelling · 2011Article
- Genotype-based dosing algorithms for warfarin therapy: data review and recommendations.Molecular diagnosis & therapy · 2011Review
- Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation.PloS one · 2011Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe application of pharmacogenetic results requires demonstrable correlations between a test result and an indicated specific course of action. We developed a computational decision-support tool that combines patient-specific genotype and phenotype information to provide strategic dosage guidance. This tool, through estimating quantitative and temporal parameters associated with the metabolism- and concentration-dependent response to warfarin, provides the necessary patient-specific context for interpreting international normalized ratio (INR) measurements.
methodsWe analyzed clinical information, plasma S-warfarin concentration, and CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genotypes for 137 patients with stable INRs. Plasma S-warfarin concentrations were evaluated by VKORC1 genotype (-1639G>A). The steady-state plasma S-warfarin concentration was calculated with CYP2C9 genotype-based clearance rates and compared with actual measurements.
resultsThe plasma S-warfarin concentration required to yield the target INR response is significantly (P < 0.05) associated with VKORC1 -1639G>A genotype (GG, 0.68 mg/L; AG, 0.48 mg/L; AA, 0.27 mg/L). Modeling of the plasma S-warfarin concentration according to CYP2C9 genotype predicted 58% of the variation in measured S-warfarin concentration: Measured [S-warfarin] = 0.67(Estimated [S-warfarin]) + 0.16 mg/L.
conclusionsThe target interval of plasma S-warfarin concentration required to yield a therapeutic INR can be predicted from the VKORC1 genotype (pharmacodynamics), and the progressive changes in S-warfarin concentration after repeated daily dosing can be predicted from the CYP2C9 genotype (pharmacokinetics). Combining the application of multivariate equations for estimating the maintenance dose with genotype-guided pharmacokinetics/pharmacodynamics modeling provides a powerful tool for maximizing the value of CYP2C9 and VKORC1 test results for ongoing application to patient care.
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