Personalized approach for direct oral anticoagulant prescription: from theory to practice

Скрипка, А. И.; Kogay, Veronika; Листратов, А. И.; Соколова, А. А.; Напалков, Д. А.; Фомин, В В

doi:10.26442/00403660.2019.07.000045

Cited by 6 publications

(1 citation statement)

References 54 publications

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“…Прямые пероральные антикоагулянты (ПОАК) имеют предсказуемый фармакокинетический профиль и лишены недостатков, присущих антагонистам витамина К [11]. Фармакологический ответ на ПОАК у разных пациентов зависит от ряда факторов, например, возраста, расы, пола, наличия вредных привычек, сопутствующих заболеваний, диеты и совместного применения с другими препаратами [12]. Однако необходимо учитывать фармакогенетические характеристики человека, которые могут повлиять на эффективность и безопасность использования ПОАК.…”

Section: введение / Introductionunclassified

Importance of using a pharmacogenetic approach to predict individual pharmacokinetics and safety profile of apixaban

Федина¹,

Sychev²,

Sychev

2022

Fgen_Fgenom

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In recent years, there has been a trend towards increased prescribing of direct-acting oral anticoagulants (DOACs) due to favourable pharmacokinetics and pharmacodynamics without the need for regular coagulation monitoring. However, recent studies have documented individual variability in plasma DOAC levels. DOAC pharmacogenetics is a relatively new area of research. There is a need to understand the role of pharmacogenetics in the adaptation of anticoagulant therapy according to a patient’s genetic characteristics. This scientific review of current data on the impact of different gene polymorphisms on apixaban pharmacokinetics broadens the understanding of the clinical relevance of genotyping for treatment efficacy and safety.

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Section: введение / Introductionunclassified

Importance of using a pharmacogenetic approach to predict individual pharmacokinetics and safety profile of apixaban

Федина¹,

Sychev²,

Sychev

2022

Fgen_Fgenom

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Hospital consumption of direct oral anticoagulants in regions of the Russian Federation in 2017–2022

Matveev,

Glagolev,

Koryanova

et al. 2024

Farm. farmakol. (Pâtigorsk)

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The aim of the study was to investigate the dynamics of inpatient consumption of direct oral anticoagulants in different regions of the Russian Federation for the period from 2017 to 2022.Materials and methods. This study is a non-interventional, retrospective analysis of the electronic database records of Cursor Marketing LLC (Russia) about the announced by medical organizations and executed contracts for the purchase of direct oral anticoagulants (DOACs). The сonsumption was calculated on the basis of a DDD (defined-daily-dose) and estimated DDDTID (defined-daily-dose/1000-inhabitants/day) for each DOACs: rivaroxaban, dabigatran and apixaban. The Rosstat database available on its official website were used as a source of inhabitants data for the Russian regions.Results. A total of 57 866 records were entered into the analyzed databases of Cursor Marketing LLC (Russia) from 2017 to 2022, 47.38% of which indicated rivaroxaban as the drug being procured, 26.51% indicated dabigatran, and 26.11% indicated apixaban. Edoxaban was not procured by healthcare organizations. During the period investigated, there was an increase in the consumption of all DOACs studied, with a higher increase for apixaban (by an average of 284.6% per year), then rivaroxaban (by 144.8% per year) and, to a lesser extent, dabigatran (by 92.5% per year). The analysis of DOACs consumption in general showed that compared to 2017, the need for these drugs in medical organizations in 2022 increased by 18 times. The Urals Federal District consistently exceeds the national average in terms of DDTID consumption. Noteworthy is the consumption dynamics of the regions of the Central Federal District and the North-Western Federal District, which made it possible to achieve DDDTID values above the national average for 5 out of 6 observation years. The lowest rates of DOACs consumption were observed in the Volga Federal District, which, despite positive growth dynamics, failed to reach the national average values. A high level of consumption (>10 DDDTID) of rivaroxaban was noted for the Arkhangelsk region (2018) and the Nenets Autonomous District (in 2021), dabigatran – only for the Arkhangelsk region (in 2018). Many more regions reached high levels of the apixaban consumption, especially in 2021.Conclusion. Despite a number of limitations, the data on the volume of DOACs procurement can be used in the analysis of the consumption at both regional and national levels. When analyzing the DOACs consumption, the impact of COVID-19 pandemic and pharmacogenetic features of patients in different regions should be taken into account. During the studied period of time, a significant part of the Russian regions achieved a consumption level of rivaroxaban and apixaban, but not dabigatran, exceeding 1 DDDTID.

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Pharmacokinetics and Pharmacogenetics of Apixaban

Savinova

Добродеева

Петрова

et al. 2020

Racionalʹnaâ farmakoterapiâ v kardiologii

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Apixaban is oral anticoagulant, it is widely used in prevention of stroke in non-valvular atrial fibrillation and treatment of deep vein thrombosis and pulmonary embolism. Its main mechanism of action is through reversible inhibition of factor Xa. It specifically binds and inhibits both free and bound factor Xa which ultimately results in reduction in the levels of thrombin formation. Apixaban is mainly metabolized by CYP3A4 with minor contributions from CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP2J2 isoenzymes. Some of the major metabolic pathways of apixaban include o-demethylation, hydroxylation, and sulfation, with o-demethylapixabansulphate being the major metabolite. The aim of this review is analysis of associated researches of single nucleotide variants (SNV) of CYP3A5 and SULT1A1 genes and search for new candidate genes reflecting effectiveness and safety of apixaban. The search for full-text publications in Russian and English languages containing key words “apixaban”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of apixaban are considered in this review. The hypothesis about CYP и SULT1A enzymes influence on apixaban metabolism was examined. To date, numerous SNVs of the CYP3A5 and SULT1A1 genes have been identified, but their potential influence on pharmacokinetics apixaban in clinical practice needs to be further studies. The role of SNVs of other genes encoding beta-oxidation enzymes of apixaban (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2J2) and transporter proteins (ABCB1, ABCG2) in its efficacy and safety are not well understood, and ABCB1 and ABCG2 genes may be potential candidate genes for studies of the drug safety.

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Personalized approach for direct oral anticoagulant prescription: from theory to practice

Cited by 6 publications

References 54 publications

Importance of using a pharmacogenetic approach to predict individual pharmacokinetics and safety profile of apixaban

Importance of using a pharmacogenetic approach to predict individual pharmacokinetics and safety profile of apixaban

Hospital consumption of direct oral anticoagulants in regions of the Russian Federation in 2017–2022

Pharmacokinetics and Pharmacogenetics of Apixaban

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