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Клинико-фармакологическое обоснование вариабельности антиагрегантного ответа при использовании разных лекарственных форм ацетилсалициловой кислоты
Зырянов С.К., Бутранова О.И. Клинико-фармакологическое обоснование вариабельности антиагрегантного ответа при использовании разных лекарственных форм ацетилсалициловой кислоты. Consilium Medicum. 2017; 19 (10): 105–112. DOI: 10.26442/2075-1753_19.10.105-112
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Zyryanov S.K., Butranova O.I. Clinico-pharmacological substantiation of antiplatelet response variability with use of different dosage forms of acetylsalicylic acid. Consilium Medicum. 2017; 19 (10): 105–112. DOI: 10.26442/2075-1753_19.10.105-112
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Аннотация
Ацетилсалициловая кислота (АСК) является наиболее распространенным антиагрегантом для профилактики сердечно-сосудистых заболеваний, включенным в современные международные и российские клинические рекомендации. С целью оптимизации профиля безопасности АСК были созданы разные лекарственные формы, в частности, кишечнорастворимая форма АСК (КР-АСК). Исследования, посвященные сравнительной эффективности и безопасности применения АСК немедленного высвобождения и КР-АСК, выявили случаи неэффективности применения АСК, интерпретируемые как резистентность к АСК. Результаты проведенных исследований свидетельствуют о минимальной частоте истинной резистентности к АСК: большинство случаев неэффективности антиагрегантной терапии АСК связаны с явлением псевдорезистентности, в основе которого лежит снижение величины биодоступности КР-АСК.
Ключевые слова: ацетилсалициловая кислота, кишечнорастворимая форма ацетилсалициловой кислоты, желудочнорастворимая форма ацетилсалициловой кислоты, фармакокинетика ацетилсалициловой кислоты, фармакодинамические эффекты ацетилсалициловой кислоты, антиагрегантная терапия, профилактика сердечно-сосудистых заболеваний.
Ключевые слова: ацетилсалициловая кислота, кишечнорастворимая форма ацетилсалициловой кислоты, желудочнорастворимая форма ацетилсалициловой кислоты, фармакокинетика ацетилсалициловой кислоты, фармакодинамические эффекты ацетилсалициловой кислоты, антиагрегантная терапия, профилактика сердечно-сосудистых заболеваний.
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Acetylsalicylic acid (ASA) is the most common antiaggregant for the prevention of cardiovascular disease, included in current international and Russian clinical guidelines. In order to optimize the safety profile of ASA, several different dosage forms have been created, in particular, the enteric-coated form of ASA (ECA). Studies on the relative efficacy and safety of immediate-release ASA and ECA have revealed cases of ASA therapy failure, defined as aspirin resistance. The results of the conducted studies indicate the minimum accidence of true aspirin resistance: most cases of ASA ineffectiveness as antiaggregant were associated with the phenomenon of pseudoresistance, which is based mainly on a decrease of the value of enteric-coated ASA bioavailability.
Key words: acetylsalicylic acid, enteric coated aspirin, plain aspirin, pharmacokinetics of acetylsalicylic acid, pharmacodynamic effects of acetylsalicylic acid, antiaggregant therapy, prophylaxis of cardiovascular diseases.
Полный текст
Список литературы
1. Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA 2007; 297 (18): 2018–24.
2. Gum PA, Kottke-Marchant K, Welsh PA et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961–5.
3. Bhatt DL, Chew DP, Hirsch AT et al. Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery. Circulation 2001; 103: 363–8.
4. Chen W-H, Lee PY, Ng W et al. Prevalence, profile, and predictors of aspirin resistance measured by the Ultegra rapid platelet function assay-ASA in patients with coronary artery disease. J Am Coll Cardiol 2005; 45: 382A.
5. Wang TH, Bhatt DL, Topol EJ. Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 2006; 27: 647–54.
6. Eikelboom JW, Hirsh J, Weitz JI et al. Aspirinresistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105: 1650–5.
7. Grundmann K, Jaschonek K, Kleine B et al. Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol 2003; 250: 63–6.
8. Patrono C, Coller B, Fitzgerald GA et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest 2004; 126: 234S–64.
9. Feletou M, Huang Y, Vanhoutte PM. Endothelium-mediated control of vascular tone: COX-1 and COX-2 products. Br J Pharmacol 2011; 164 (3): 894–912.
10. Cheng Y, Wang M, Yu Y et al. Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J Clin Invest 2006; 116: 1391–9.
11. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 1998; 38: 97–120.
12. Batoule H, Majed and Raouf A. Khalil. Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn. Pharmacol Rev 64: A–AQ, 2012.
13. Hennekens CH, Schneider WR, Pokov A et al. A randomized trial of aspirin at clinically relevant doses and nitric oxide formation in humans. J Cardiovasc Pharmacol Ther 2010; 15 (4): 344–8.
14. Hetzel S, DeMets D, Schneider R et al. Aspirin increases nitric oxide formation in chronic stable coronary disease. J Cardiovasc Pharmacol Ther 2013; 18 (3): 217–21.
15. Ball SK, Field MC, Tippins JR. Regulation of thromboxane receptor signaling at multiple levels by oxidative stress-induced stabilization, relocation and enhanced responsiveness. PLoS ONE 2010; 5 (9): e12798.
16. Muzaffar S, Shukla N, Massey Y et al. NADPH oxidase 1 mediates upregulation of thromboxane A2 synthase in human vascular smooth muscle cells: inhibition with iloprost. Eur J Pharmacol 2011; 658 (2–3): 187–92.
17. Zhang M, Song P, Xu J, Zou MH. Activation of NAD(P)H oxidases by thromboxane A2 receptor uncouples endothelial nitric oxide synthase. Arterioscler Thromb Vasc Biol 2011; 31 (1): 125–32.
18. Schror K, Rauch BH. Aspirin and lipid mediators in the cardiovascular system. Prostaglandins Lipid Mediators 2015; 121 (Pt. A): 17–23.
19. Romano M, Cianci E, Simiele F, Recchiuti A. Lipoxins and aspirin-triggered lipoxins in resolution of inflammation. Eur J Pharmacol 2015; 760: 49–63.
20. Ho KJ, Spite M, Owens CD et al. Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol 2010; 177 (4): 2116–23.
21. Vital SA, Becker F, Holloway PM et al. Formyl-peptide receptor 2/3/Lipoxin a4 receptor regulates neutrophil-platelet aggregation and attenuates cerebral inflammation: impact for therapy in cardiovascular disease. Circulation 2016; 133 (22): 2169–79.
22. Gil-Villa AM, Norling LV, Serhan CN et al. Aspirin triggered-lipoxin A4 reduces the adhesion of human polymorphonuclear neutrophils to endothelial cells initiated by preeclamptic plasma. Prostaglandins Leukot Essent Fat Acids 2012; 87 (4–5): 127–34.
23. Dona M, Fredman G, Schwab JM et al. Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood 2008; 112 (3): 848–55.
24. Gong Y, Lin M, Piao L et al. Aspirin enhances protective effect of fish oil against thrombosis and injury-induced vascular remodelling. Br J Pharmacol 2015; 172 (23): 5647–60.
25. Pearson TA, Blair SN et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patient without Coronary or other Atherosclerotic Vascular Diseases. Circulation 2002; 106: 388–91.
26. Campbell CL, Smyth S, Montalescot G et al. Aspirin Dose for the Prevention of Cardiovascular Disease A Systematic Review. JAMA 2007; 297: 2018–24.
27. Michelson AD, Cattaneo M, Eikelboom JW et al. Aspirin Resistance: Position Paper of the Working Group on Aspirin Resistance, Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2005; 3: 1–3.
28. Nagelschmitz J, Blunck, M, Kraetzschmar J et al. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers. Clin Pharmacol 2014; 6: 51–9.
29. Bhatt DL, Grosser T, Jing-fei Dong et al. Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus. J American Col Cardiol 2017; 69 (6): 603–12.
30. Grosser T, Fries S, Lawson JA, Kapoor SC et al. Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin. Circulation 2013; 127 (3): 377–85.
31. Cox D, Maree AO, Dooley M et al. Effect of Enteric Coating on Antiplatelet Activity of Low-Dose Aspirin in Healthy Volunteers. Stroke 2006; 37: 2153–8.
32. Haastrup PF, Grønlykke T, Dorte Ejg Jarbøl. Enteric Coating Can Lead to Reduced Antiplatelet Effect of Low-Dose Acetylsalicylic Acid. Basic Clin Pharmacol Toxicol 2015; 116: 212–5.
2. Gum PA, Kottke-Marchant K, Welsh PA et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961–5.
3. Bhatt DL, Chew DP, Hirsch AT et al. Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery. Circulation 2001; 103: 363–8.
4. Chen W-H, Lee PY, Ng W et al. Prevalence, profile, and predictors of aspirin resistance measured by the Ultegra rapid platelet function assay-ASA in patients with coronary artery disease. J Am Coll Cardiol 2005; 45: 382A.
5. Wang TH, Bhatt DL, Topol EJ. Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 2006; 27: 647–54.
6. Eikelboom JW, Hirsh J, Weitz JI et al. Aspirinresistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105: 1650–5.
7. Grundmann K, Jaschonek K, Kleine B et al. Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol 2003; 250: 63–6.
8. Patrono C, Coller B, Fitzgerald GA et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest 2004; 126: 234S–64.
9. Feletou M, Huang Y, Vanhoutte PM. Endothelium-mediated control of vascular tone: COX-1 and COX-2 products. Br J Pharmacol 2011; 164 (3): 894–912.
10. Cheng Y, Wang M, Yu Y et al. Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J Clin Invest 2006; 116: 1391–9.
11. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 1998; 38: 97–120.
12. Batoule H, Majed and Raouf A. Khalil. Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn. Pharmacol Rev 64: A–AQ, 2012.
13. Hennekens CH, Schneider WR, Pokov A et al. A randomized trial of aspirin at clinically relevant doses and nitric oxide formation in humans. J Cardiovasc Pharmacol Ther 2010; 15 (4): 344–8.
14. Hetzel S, DeMets D, Schneider R et al. Aspirin increases nitric oxide formation in chronic stable coronary disease. J Cardiovasc Pharmacol Ther 2013; 18 (3): 217–21.
15. Ball SK, Field MC, Tippins JR. Regulation of thromboxane receptor signaling at multiple levels by oxidative stress-induced stabilization, relocation and enhanced responsiveness. PLoS ONE 2010; 5 (9): e12798.
16. Muzaffar S, Shukla N, Massey Y et al. NADPH oxidase 1 mediates upregulation of thromboxane A2 synthase in human vascular smooth muscle cells: inhibition with iloprost. Eur J Pharmacol 2011; 658 (2–3): 187–92.
17. Zhang M, Song P, Xu J, Zou MH. Activation of NAD(P)H oxidases by thromboxane A2 receptor uncouples endothelial nitric oxide synthase. Arterioscler Thromb Vasc Biol 2011; 31 (1): 125–32.
18. Schror K, Rauch BH. Aspirin and lipid mediators in the cardiovascular system. Prostaglandins Lipid Mediators 2015; 121 (Pt. A): 17–23.
19. Romano M, Cianci E, Simiele F, Recchiuti A. Lipoxins and aspirin-triggered lipoxins in resolution of inflammation. Eur J Pharmacol 2015; 760: 49–63.
20. Ho KJ, Spite M, Owens CD et al. Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol 2010; 177 (4): 2116–23.
21. Vital SA, Becker F, Holloway PM et al. Formyl-peptide receptor 2/3/Lipoxin a4 receptor regulates neutrophil-platelet aggregation and attenuates cerebral inflammation: impact for therapy in cardiovascular disease. Circulation 2016; 133 (22): 2169–79.
22. Gil-Villa AM, Norling LV, Serhan CN et al. Aspirin triggered-lipoxin A4 reduces the adhesion of human polymorphonuclear neutrophils to endothelial cells initiated by preeclamptic plasma. Prostaglandins Leukot Essent Fat Acids 2012; 87 (4–5): 127–34.
23. Dona M, Fredman G, Schwab JM et al. Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood 2008; 112 (3): 848–55.
24. Gong Y, Lin M, Piao L et al. Aspirin enhances protective effect of fish oil against thrombosis and injury-induced vascular remodelling. Br J Pharmacol 2015; 172 (23): 5647–60.
25. Pearson TA, Blair SN et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patient without Coronary or other Atherosclerotic Vascular Diseases. Circulation 2002; 106: 388–91.
26. Campbell CL, Smyth S, Montalescot G et al. Aspirin Dose for the Prevention of Cardiovascular Disease A Systematic Review. JAMA 2007; 297: 2018–24.
27. Michelson AD, Cattaneo M, Eikelboom JW et al. Aspirin Resistance: Position Paper of the Working Group on Aspirin Resistance, Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2005; 3: 1–3.
28. Nagelschmitz J, Blunck, M, Kraetzschmar J et al. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers. Clin Pharmacol 2014; 6: 51–9.
29. Bhatt DL, Grosser T, Jing-fei Dong et al. Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus. J American Col Cardiol 2017; 69 (6): 603–12.
30. Grosser T, Fries S, Lawson JA, Kapoor SC et al. Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin. Circulation 2013; 127 (3): 377–85.
31. Cox D, Maree AO, Dooley M et al. Effect of Enteric Coating on Antiplatelet Activity of Low-Dose Aspirin in Healthy Volunteers. Stroke 2006; 37: 2153–8.
32. Haastrup PF, Grønlykke T, Dorte Ejg Jarbøl. Enteric Coating Can Lead to Reduced Antiplatelet Effect of Low-Dose Acetylsalicylic Acid. Basic Clin Pharmacol Toxicol 2015; 116: 212–5.
________________________________________________
1. Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA 2007; 297 (18): 2018–24.
2. Gum PA, Kottke-Marchant K, Welsh PA et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961–5.
3. Bhatt DL, Chew DP, Hirsch AT et al. Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery. Circulation 2001; 103: 363–8.
4. Chen W-H, Lee PY, Ng W et al. Prevalence, profile, and predictors of aspirin resistance measured by the Ultegra rapid platelet function assay-ASA in patients with coronary artery disease. J Am Coll Cardiol 2005; 45: 382A.
5. Wang TH, Bhatt DL, Topol EJ. Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 2006; 27: 647–54.
6. Eikelboom JW, Hirsh J, Weitz JI et al. Aspirinresistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105: 1650–5.
7. Grundmann K, Jaschonek K, Kleine B et al. Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol 2003; 250: 63–6.
8. Patrono C, Coller B, Fitzgerald GA et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest 2004; 126: 234S–64.
9. Feletou M, Huang Y, Vanhoutte PM. Endothelium-mediated control of vascular tone: COX-1 and COX-2 products. Br J Pharmacol 2011; 164 (3): 894–912.
10. Cheng Y, Wang M, Yu Y et al. Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J Clin Invest 2006; 116: 1391–9.
11. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 1998; 38: 97–120.
12. Batoule H, Majed and Raouf A. Khalil. Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn. Pharmacol Rev 64: A–AQ, 2012.
13. Hennekens CH, Schneider WR, Pokov A et al. A randomized trial of aspirin at clinically relevant doses and nitric oxide formation in humans. J Cardiovasc Pharmacol Ther 2010; 15 (4): 344–8.
14. Hetzel S, DeMets D, Schneider R et al. Aspirin increases nitric oxide formation in chronic stable coronary disease. J Cardiovasc Pharmacol Ther 2013; 18 (3): 217–21.
15. Ball SK, Field MC, Tippins JR. Regulation of thromboxane receptor signaling at multiple levels by oxidative stress-induced stabilization, relocation and enhanced responsiveness. PLoS ONE 2010; 5 (9): e12798.
16. Muzaffar S, Shukla N, Massey Y et al. NADPH oxidase 1 mediates upregulation of thromboxane A2 synthase in human vascular smooth muscle cells: inhibition with iloprost. Eur J Pharmacol 2011; 658 (2–3): 187–92.
17. Zhang M, Song P, Xu J, Zou MH. Activation of NAD(P)H oxidases by thromboxane A2 receptor uncouples endothelial nitric oxide synthase. Arterioscler Thromb Vasc Biol 2011; 31 (1): 125–32.
18. Schror K, Rauch BH. Aspirin and lipid mediators in the cardiovascular system. Prostaglandins Lipid Mediators 2015; 121 (Pt. A): 17–23.
19. Romano M, Cianci E, Simiele F, Recchiuti A. Lipoxins and aspirin-triggered lipoxins in resolution of inflammation. Eur J Pharmacol 2015; 760: 49–63.
20. Ho KJ, Spite M, Owens CD et al. Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol 2010; 177 (4): 2116–23.
21. Vital SA, Becker F, Holloway PM et al. Formyl-peptide receptor 2/3/Lipoxin a4 receptor regulates neutrophil-platelet aggregation and attenuates cerebral inflammation: impact for therapy in cardiovascular disease. Circulation 2016; 133 (22): 2169–79.
22. Gil-Villa AM, Norling LV, Serhan CN et al. Aspirin triggered-lipoxin A4 reduces the adhesion of human polymorphonuclear neutrophils to endothelial cells initiated by preeclamptic plasma. Prostaglandins Leukot Essent Fat Acids 2012; 87 (4–5): 127–34.
23. Dona M, Fredman G, Schwab JM et al. Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood 2008; 112 (3): 848–55.
24. Gong Y, Lin M, Piao L et al. Aspirin enhances protective effect of fish oil against thrombosis and injury-induced vascular remodelling. Br J Pharmacol 2015; 172 (23): 5647–60.
25. Pearson TA, Blair SN et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patient without Coronary or other Atherosclerotic Vascular Diseases. Circulation 2002; 106: 388–91.
26. Campbell CL, Smyth S, Montalescot G et al. Aspirin Dose for the Prevention of Cardiovascular Disease A Systematic Review. JAMA 2007; 297: 2018–24.
27. Michelson AD, Cattaneo M, Eikelboom JW et al. Aspirin Resistance: Position Paper of the Working Group on Aspirin Resistance, Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2005; 3: 1–3.
28. Nagelschmitz J, Blunck, M, Kraetzschmar J et al. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers. Clin Pharmacol 2014; 6: 51–9.
29. Bhatt DL, Grosser T, Jing-fei Dong et al. Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus. J American Col Cardiol 2017; 69 (6): 603–12.
30. Grosser T, Fries S, Lawson JA, Kapoor SC et al. Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin. Circulation 2013; 127 (3): 377–85.
31. Cox D, Maree AO, Dooley M et al. Effect of Enteric Coating on Antiplatelet Activity of Low-Dose Aspirin in Healthy Volunteers. Stroke 2006; 37: 2153–8.
32. Haastrup PF, Grønlykke T, Dorte Ejg Jarbøl. Enteric Coating Can Lead to Reduced Antiplatelet Effect of Low-Dose Acetylsalicylic Acid. Basic Clin Pharmacol Toxicol 2015; 116: 212–5.
Авторы
С.К.Зырянов*, О.И.Бутранова
ФГАОУ ВО «Российский университет дружбы народов». 117198, Россия, Москва, ул. Миклухо-Маклая, д. 6
*sergey.k.zyryanov@gmail.com
ФГАОУ ВО «Российский университет дружбы народов». 117198, Россия, Москва, ул. Миклухо-Маклая, д. 6
*sergey.k.zyryanov@gmail.com
________________________________________________
S.K.Zyryanov*, O.I.Butranova
People’s Friendship University of Russia. 117198, Russian Federation, Moscow, ul. Miklukho-Maklaia, d. 6
*sergey.k.zyryanov@gmail.com
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