Vitamin K metabolism in a patient resistant to vitamin K antagonists.

Détails

ID Serval
serval:BIB_1A6EC04AB1FE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Vitamin K metabolism in a patient resistant to vitamin K antagonists.
Périodique
Haemostasis
Auteur⸱e⸱s
Keréveur A., Leclercq M., Trossaërt M., Dupeyron J.P., Parent F., Horellou M.H., Conard J., Bachmann F., Samama M.M.
ISSN
0301-0147 (Print)
ISSN-L
0301-0147
Statut éditorial
Publié
Date de publication
1997
Peer-reviewed
Oui
Volume
27
Numéro
4
Pages
168-173
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Résumé
We investigated various pharmacokinetic and pharmacodynamic parameters in a 63-year-old man, resistant to warfarin, fluindione, acenocoumarol and phenprocoumon. Daily doses of up to 30 mg of the long-acting phenprocoumon yielded a drug concentration of 85 mg/l (usual range 1-5 mg/l) but the international normalized ratio remained around 1. The plasma half-life of phenprocoumon was approximately 350 h (normal 120-150 h). Thus, the resistance was not due to malabsorption or to an accelerated metabolism of the drug. The level of vitamin K1 (1,202 ng/l) was insufficient to induce resistance. Decarboxyprothrombin concentrations were low, demonstrating that the gamma-carboxylation of the precursors of the vitamin K-dependent coagulation factors was not effectively reduced. The concentration of vitamin K epoxide, normally increased under oral anticoagulation, correlated to the vitamin K concentration (r2 = 0.77) but the quotient epoxide/vitamin K remained 4-fold lower than that of 22 warfarin-sensitive patients, suggesting an absence of blockade of the vitamin K reductase by phenprocoumon. This resistance to all the molecular forms of the vitamin K antagonists is most likely due to a reduced affinity of the drugs to a mutant vitamin K reductase.
Mots-clé
Drug Resistance, Half-Life, Humans, Male, Middle Aged, NAD(P)H Dehydrogenase (Quinone)/antagonists & inhibitors, Phenprocoumon/blood, Vitamin K/antagonists & inhibitors, Vitamin K/blood, Vitamin K/metabolism, Vitamin K 1/blood, Warfarin/blood
Pubmed
Web of science
Création de la notice
18/05/2014 20:17
Dernière modification de la notice
08/06/2024 6:58
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