Therapeutic Dosing of Acenocoumarol: Proposal of a Population Specific Pharmacogenetic Dosing Algorithm and Its Validation in North Indians

@article{Rathore2012TherapeuticDO,
  title={Therapeutic Dosing of Acenocoumarol: Proposal of a Population Specific Pharmacogenetic Dosing Algorithm and Its Validation in North Indians},
  author={Saurabh Singh Rathore and Surendra Kumar Agarwal and Shantanu Pande and Sushil Kumar Singh and Tulika Mittal and Balraj Mittal},
  journal={PLoS ONE},
  year={2012},
  volume={7}
}
Objectives To develop a population specific pharmacogenetic acenocoumarol dosing algorithm for north Indian patients and show its efficiency in dosage prediction. Methods Multiple and linear stepwise regression analyses were used to include age, sex, height, weight, body surface area, smoking status, VKORC1 -1639 G>A, CYP4F2 1347 G>A, CYP2C9*2,*3 and GGCX 12970 C>G polymorphisms as variables to generate dosing algorithms. The new dosing models were compared with already reported algorithms and… 

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References

SHOWING 1-10 OF 47 REFERENCES
Optimization of warfarin dose by population-specific pharmacogenomic algorithm
TLDR
This population-specific algorithm has greater clinical utility in optimizing the warfarin dose, thereby decreasing the adverse effects of suboptimal dose.
Pharmacogenetic relevance of CYP4F2 V433M polymorphism on acenocoumarol therapy.
TLDR
The data underline the relevant role of CYP4F2 V433M polymorphism in the pharmacogenetics of coumarin anticoagulants and highlight the need to continue to evaluate its influence in earliest response to acenocoumarol.
Loading and maintenance dose algorithms for phenprocoumon and acenocoumarol using patient characteristics and pharmacogenetic data.
TLDR
These are the first genotype-guided loading and maintenance dose algorithms for PHE and ACE using large cohorts and the utility of these algorithms will be tested in randomized controlled trials.
Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin
TLDR
The goal was to develop and validate a pharmacogenetic algorithm that explained 53–54% of the variability in the warfarin dose in the derivation and validation cohorts.
Prospective Study of Warfarin Dosage Requirements Based on CYP2C9 and VKORC1 Genotypes
TLDR
It is demonstrated that pharmacogenetics‐based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.
Pharmacogenetics of acenocoumarol in patients with extreme dose requirements
TLDR
Two clinical data, age and BSA, and three SNPs in the VKORC1, CYP2C9 and CYP4F2 genes strongly predict outlier patients treated with acenocoumarol.
Estimation of the warfarin dose with clinical and pharmacogenetic data.
TLDR
The use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are significantly closer to the required stable therapeutic dose than those derived from a clinical algorithm or a fixed-dose approach.
VKORC1 and CYP2C9 polymorphisms are associated with warfarin dose requirements in Turkish patients
TLDR
Polymorphisms in VKORC1 and CYP2C9 genes were important determinants of warfarin dose requirements in Turkish patients and needed a 40% lower mean weekly warFarin dose compared to wild types.
The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen.
TLDR
The multivariate regression model including the variables of age, CYP2C9 and VKORC1 genotype, and height produced the best model for estimating warfarin dose (R2 = 55%).
Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients
TLDR
It is anticipated that the use of dosing regimens modified by taking into account the contribution of age, weight, and the CYP2C9 and VKORC1 genotypes has the potential to improve the safety of warfarin therapy.
...
1
2
3
4
5
...