| Title | Evidence for a pharmacogenetic adapted dose of oral anticoagulant in routine medical practice. | | Author(s) | Becquemont L | | Institution | Pharmacology Department, Faculté de médecine Paris Sud, Université Paris-Sud, Le Kremlin Bicêtre, France. laurent.becquemont@bct.ap-hop-paris.fr | | Source | Eur J Clin Pharmacol 2008 Oct; 64(10):953-60. | | MeSH | Acenocoumarol
Administration, Oral
Algorithms
Anticoagulants
Aryl Hydrocarbon Hydroxylases
Dose-Response Relationship, Drug
Humans
International Normalized Ratio
Mixed Function Oxygenases
Pharmacogenetics
Phenprocoumon
Polymorphism, Genetic
Randomized Controlled Trials as Topic
Warfarin
| | Abstract | Oral anticoagulants (OA) are a leading cause of fatal haemorrhagic adverse events in relation with an important interindividual variability of response to these drugs. Besides several clinical factors, this interindividual variability of response to OA has a pharmacogenetic basis. Carriers of cytochrome P450 2C9 (CYP2C9)-deficient alleles have a reduced clearance of warfarin and are exposed to dramatic overdoses in the first weeks of treatment. Genetic polymorphisms of vitamin K epoxide reductase (VKORC1), the target of OA, identify patients with a high sensitivity to OA who are at risk of early overdose. Most pharmacogenetic evidence is presently restricted to warfarin. Several warfarin dosing algorithms have been constructed, adapted on CYP2C9 and VKORC1 genotypes and clinical factors, to predict the best dose for each patient. Carriers of one of allelic variant need a 20-30% reduction of warfarin dose. However, definite evidence concerning the usefulness of these algorithms in terms of reducing the frequency of major bleeding episodes is still lacking. Ongoing prospective randomised trials will ascertain definitive answer over the coming years. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
Review
| | PubMed ID | 18758764 |
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