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Titre du document / Document title

Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon

Auteur(s) / Author(s)

BEINEMA Maarten (1) ; BROUWERS Jacobus R. B. J. (2) ; SCHALEKAMP Tom (3) ; WILFFERT Bob (2) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Thrombosis Centre, Deventer Hospital, Deventer, PAYS-BAS
(2) Department of Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, PAYS-BAS
(3) Division of Pharmacoepidemiology and Pharmacotherapy, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, PAYS-BAS

Résumé / Abstract

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 the VKORCI 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 andVKORC I genotype is most significant during the initial period of coumarin anticoagulant therapy.The effect ofVKORC I 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 anticoagulation. Pharmacogenetic testing before initiating coumarin oral anticoagulants may add to the safety of all coumarin anticoagulants especially in the elderly receiving multiple drugs.

Revue / Journal Title

Thrombosis and haemostasis    ISSN  0340-6245   CODEN THHADQ 

Source / Source

2008, vol. 100, no6, pp. 1052-1057 [6 page(s) (article)] (69 ref.)

Langue / Language

Anglais

Editeur / Publisher

Schattauer, Stuttgart, ALLEMAGNE  (1976) (Revue)

Mots-clés anglais / English Keywords

Coumarine derivatives

;

Antivitamin K

;

Genetics

;

Pharmacodynamics

;

Chemotherapy

;

Phenprocoumon

;

Anticoagulant

;

Treatment

;

Acenocoumarol

;

Clinical trial

;

Pharmacogenetics

;

Warfarin

;

Mots-clés français / French Keywords

Dérivé de la coumarine

;

Antivitamine K

;

Génétique

;

Pharmacodynamie

;

Chimiothérapie

;

Phenprocoumone

;

Anticoagulant

;

Traitement

;

Acénocoumarol

;

Essai clinique

;

Pharmacogénétique

;

Warfarine

;

Mots-clés espagnols / Spanish Keywords

Antivitamina K

;

Genética

;

Farmacodinámica

;

Quimioterapia

;

Fenprocumon

;

Anticoagulante

;

Tratamiento

;

Acenocumarol

;

Ensayo clínico

;

Farmacogenética

;

Warfarina

;

Mots-clés d'auteur / Author Keywords

Clinical trials

;

oral anticoagulants

;

pharamacogenetics

;

pharmacodynamics

;

Localisation / Location

INIST-CNRS, Cote INIST : 10255, 35400018511056.0160

Nº notice refdoc (ud4) : 20994112



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