E.G. Komova (1,2), V.A. Vavilin (1), M.K. Ivanov (2), V.V. Lyakhovich (1) 1 -Research Institute of Molecular Biology and Biophysics, Timakova str., 2/12, Novosibirsk, 630060, Russian Federation; 2 -StockJoint Company «Vector-Best», Pasechnaya str., 3, Novosibirsk, 630128, Russian Federation

The review highlights the problem of the influence of the genetic characteristics of patients in the dosage of anticoagulant drugs, the main adverse reaction of taking of which is the internal bleeding. Therapy with anticoagulant drugs is characterized by a wide interindividual variability in the effective dose (from 0,5 to 20 mg/day of warfarin), accompanied by side effects such as bleeding (15% of the total cases receiving the therapy) or vice versa, resistance (about 1%). Molecular target and drug-metabolizing proteins, the functional significance of polymorphic variants of the genes encoding these proteins and the decisive contribution of genetic factors to the pharmacokinetics and pharmacodynamics of these drugs were established by the studies over the last 20 years. The search for new anticoagulant drugs has not yet given rise in the discovery of compounds that would be free from the activity of these enzymes. Therefore, at this time the way out is the use of pharmacogenetic tests in the administration of anticoagulant drugs to determine the individual dose, depending on the genetic characteristics of the patient. There was well developed the pharmacogenetic approach in the choice of a dose of warfarin, which is safer for patients and pharmaco-effective if compared with the traditional method of dose detection. In the review there are considered key works, including the history of the issue, in terms of the use of this knowledge in aims of predictive genetic testing for personalized anticoagulation therapy.
anticoagulants, warfarin, cytochromes P450, vitamin K epoxid reductase complex subunit 1, genetic polymorphism

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