Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon

Maarten Beinema; Jacobus R. B. J. Brouwers; Tom Schalekamp; Bob Wilffert

doi:10.1160/TH08-04-0116

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(06): 1052-1057
DOI: 10.1160/TH08-04-0116

Review Article

Schattauer GmbH

Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon

Maarten Beinema

¹Thrombosis Centre, Deventer Hospital, Deventer, The Netherlands

,

Jacobus R. B. J. Brouwers

²Department of Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, The Netherlands

,

Tom Schalekamp

³Division of Pharmacoepidemiology and Pharmacotherapy, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

,

Bob Wilffert

²Department of Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, The Netherlands

› Author Affiliations

Abstract

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Summary

Coumarin oral anticoagulant drugs have proven to be effective for the prevention of thromboembolic events. World-wide, warfarin is the most prescribed drug. In Europe, acenocoumarol and phenprocoumon are also administered. Yet it has been proven that variant alleles of theVKORC1 and CYP2C9 genotypes influence the pharmacokinetics and pharmacodynamics of these drugs. The combination of these two variant genotypes is a major cause of the inter-individual differences in coumarin anticoagulant drug dosage. Individuals who test positive for both variant genotypes are at increased risk of major bleeding. The impact of the CYP2C9 andVKORC1 genotype is most significant during the initial period of coumarin anticoagulant therapy. The effect ofVKORC1 allelic variants is relatively similar for all three VKAs. The CYP2C9 polymorphism is associated with delayed stabilisation for coumarin anticoagulants. The effects of CYP2C9 polymorphisms on the pharmacokinetics and anticoagulant response are least pronounced in the case of phenprocoumon. In the long term, patients using phenprocoumon have more often international normalised ratio (INR) values in the therapeutic range, requiring fewer monitoring visits. This leads us to conclude that in the absence of pharmacogenetic testing, phenprocoumon seems preferable for use in long-term therapeutic anti-coagulation. Pharmacogenetic testing before initiating coumarin oral anticoagulants may add to the safety of all coumarin anticoagulants especially in the elderly receiving multiple drugs.

Keywords

Clinical trials - oral anticoagulants - pharamacogenetics - pharmacodynamics

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References

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