Клинико-фармакологические аспекты применения витамина D: от известных фактов к поиску новых мишеней
Клинико-фармакологические аспекты применения витамина D: от известных фактов к поиску новых мишеней
Климова О.Ю., Бердникова Н.Г., Казаков Р.Е. Клинико-фармакологические аспекты применения витамина D: от известных фактов к поиску новых мишеней. Consilium Medicum. 2016; 18 (2): 109–116. DOI: 10.26442/2075-1753_2016.2.109-116
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Klimova O.Yu., Berdnikova N.G., Kazakov R.E. Clinical and pharmacological aspects of the use of vitamin D: from the known facts to look for new targets. Consilium Medicum. 2016; 18 (2): 109–116. DOI: 10.26442/2075-1753_2016.2.109-116
Клинико-фармакологические аспекты применения витамина D: от известных фактов к поиску новых мишеней
Климова О.Ю., Бердникова Н.Г., Казаков Р.Е. Клинико-фармакологические аспекты применения витамина D: от известных фактов к поиску новых мишеней. Consilium Medicum. 2016; 18 (2): 109–116. DOI: 10.26442/2075-1753_2016.2.109-116
________________________________________________
Klimova O.Yu., Berdnikova N.G., Kazakov R.E. Clinical and pharmacological aspects of the use of vitamin D: from the known facts to look for new targets. Consilium Medicum. 2016; 18 (2): 109–116. DOI: 10.26442/2075-1753_2016.2.109-116
Витамин D не только занимает важнейшее место в регуляции кальциево-фосфорного гомеостаза, но и обладает множеством «внекостных» эффектов. Выявленная в эпидемиологических исследованиях взаимосвязь между дефицитом витамина D и развитием разных заболеваний в настоящее время проходит изучение в рандомизированных клинических исследованиях. Выраженность клинических эффектов витамина D может зависеть от генетического полиморфизма VDR (рецепторов витамина D), экспрессирующихся более чем в 40 тканях-мишенях. Для профилактики и лечения витамин D-дефицитных состояний рекомендуются инсоляция и применение препаратов витамина D, в частности, его активного метаболита альфакальцидола.
Vitamin D not only occupies an important place in the regulation of calcium-phosphorus homeostasis, but also has many "non-bone" effects. Revealed in epidemiological studies the link between vitamin D deficiency and the development of various diseases is currently under study in randomized clinical trials. Severity of clinical effects of vitamin D may be dependent on the genetic polymorphism of VDR (vitamin receptors D), over-expressed in the 40 target tissues. For the prevention and treatment of vitamin D-deficient conditions and insolation recommended application of vitamin D, in particular, its active metabolite alfacalcidol is used.
1. Fukumoto S, Martin TJ. Bone as an endocrine organ. Trends Endocrinol Metab 2009; 20 (5): 230–6.
2. Мелентьева А.А., Барышева О.Ю., Везикова Н.Н. и др. Роль фактора роста фибробластов 23 и фактора Klotho в развитии минерально-костных нарушений при хронической болезни почек. Курский научно-практ. вестн. «Человек и его здоровье». 2014; 3: 102–9. / Melent'eva A.A., Barysheva O.Iu., Vezikova N.N. i dr. Rol' faktora rosta fibroblastov 23 i faktora Klotho v razvitii mineral'no-kostnykh narushenii pri khronicheskoi bolezni pochek. Kurskii nauchno-prakt. vestn. “Chelovek i ego zdorov'e”. 2014; 3: 102–9. [in Russian]
3. Гребенникова Т.А., Белая Ж.Е., Цориев Т.Т. и др. Эндокринная функция костной ткани. Остеопороз и остеопатии. 2015; 1: 28–37. / Grebennikova T.A., Belaia Zh.E., Tsoriev T.T. i dr. Endokrinnaia funktsiia kostnoi tkani. Osteoporoz i osteopatii. 2015; 1: 28–37. [in Russian]
4. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266–81.
5. Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr 2004; 80 (6): 1706S–1709S.
6. Holick MF, Binkley NC et al. Weaver Evaluation, Treatment, and Prevention of Vitamin D. Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrin Metab 2011; 6: 1911–30
7. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab 2010; 95: 471–8.
8. Holick MF, Binkley NC, Heike A et al. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab 2012; 97 (4): 1153–8.
9. Клинические рекомендации. Дефицит витамина D у взрослых: диагностика, лечение и профилактика. Российская Ассоциация Эндокринологов. ФГБУ «Эндокринологический Научный Центр Министерства здравоохранения РФ». М., 2015 http://www.endocrincentr.ru/images/material-images/Rek_Vit%20D_2015.pdf / Klinicheskie rekomendatsii. Defitsit vitamina D u vzroslykh: diagnostika, lechenie i profilaktika. Rossiiskaia Assotsiatsiia Endokrinologov. FGBU “Endokrinologicheskii Nauchnyi Tsentr Ministerstva zdravookhraneniia RF”. M., 2015 http://www.endocrincentr.ru/images/material-images/Rek_Vit%20D_2015.pdf [in Russian]
10. IARC Working Group on Vitamin D: Vitamin D and Cancer. Report number 5. Geneva, Switzerland, WHO Press, 2008.
11. Peterlik M, Boonen St, Cross HS, Lamberg-Allardt C. Vitamin D and Calcium Insufficiency – Related Chronic Diseases: an Emerging World-Wide Public Health Problem. J Environ Res Public Health 2009; 6 (10): 2585–607. http://dx.doi.org/10.3390/ijerph6102585
12. Grant WB, Mohr SF. Ecological studies of ultraviolet B, vitamin D and cancer since 2000. Ann Epidemiol 2009; 19: 446–54.
13. Lappe JM, Travers-Gustafson D, Davies KM et al. And calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85 (6): 1586–91.
14. Kendrick J, Targher G, Smits G, Chonchol M. 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Exam Surv Atheroscler 2009; 205 (1): 255–60.
15. Егшатян Л.В., Дудинская Е.Н., Ткачева О.Н., Каштанова Д.А. Роль витамина D в патогенезе хронических неинфекционных заболеваний. Остеопороз и остеопатии. 2014; 1: 27–30. / Egshatian L.V., Dudinskaia E.N., Tkacheva O.N., Kashtanova D.A. Rol' vitamina D v patogeneze khronicheskikh neinfektsionnykh zabolevanii. Osteoporoz i osteopatii. 2014; 1: 27–30. [in Russian]
16. Li C, Qiao G, Uskokovic M et al. Vitamin D: a negative endocrine regulator of the reninangiotensin system and blood pressure. J of Steroid Bioch and Molec Biol 2004; 89–90 (1–5): 387–92.
17. Afzal S, Nordestgaard BG. Low vitamin D and hypertension: a causal association? 2014. www.thelancet.com/diabetes-endocrinology. http://dx.doi.org/10.1016/S2213-8587(14)70119-6
18. Konradsen S, Ag H, Lindberg F et al. Serum 1.25-dihydroxy vitamin D is inversely associated with body mass index. Eur J Nutr 2008; 47 (2): 87–91.
19. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 2004; 27: 2813–8.
20. Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004; 79 (5): 820–5.
21. Harinarayan ChV. Vitamin D and diabetes mellitus. Hormones 2014; 13 (2): 163–81.
22. Вельков В.В. С-реактивный белок – в лабораторной диагностике острых воспалений и в оценке рисков сосудистых патологий. Клинико-лабораторный консилиум. 2008; 2 (21): 37–48. / Vel'kov V.V. S-reaktivnyi belok – v laboratornoi diagnostike ostrykh vospalenii i v otsenke riskov sosudistykh patologii. Kliniko-laboratornyi konsilium. 2008; 2 (21): 37–48. [in Russian]
23. Liu PT, Stenger S, Li H et al. Vitamin D3-Triggered Antimicrobial Response – Another Pleiotropic Effect beyond Mineral and Bone Metabolism. Science 2006; 311: 1770–3.
24. Chun RF, Liu NQ, Lee T et al. Vitamin D supplementation and antibacterial immune responses in adolescents and young adults with HIV/AIDS. J Steroid Biochem Mol Biol 2014; 8: 148. http://dx.doi.org/10.1016/j.jsbmb.2014.07.013
25. Skaaby T, Nystrup Husemoen LL, Thuesen BH. Vitamin D Status and Chronic Obstructive Pulmonary Disease: A Prospective General Population Study. 2014; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0090654
26. Malinovschi А, Masoero М, Bellocchia М. Severe vitamin D deficiency is associated with frequent exacerbations and hospitalization in COPD patients. http://respiratory-research.com/content/15/1/131
27. Ringe JD et al. Alfacalcidol versus plain vitamin D in the treatment of glucocorticoid/inflammation-induced osteoporosis. J Rheumatol Suppl. 2005; 76: 33–40.
28. Ringe JD, Farahmand P, Schacht E. Alfacalcidol in men with osteoporosis: a prospective, observational, 2-year trial on 214 patients. Rheumatol Int 2013; 33 (3): 637–43.
29. Скрипникова И.А. Предотвращение падений – один из способов профилактики переломов, связанных с остеопорозом. Consilium Medicum. Неврология и ревматология. (Прил.). 2014; 16 (2): 66–70. / Skripnikova I.A. Predotvrashchenie padenii – odin iz sposobov profilaktiki perelomov, sviazannykh s osteoporozom. Consilium Medicum. Neurology and Rheumatology (Suppl.). 2014; 16 (2): 66–70. [in Russian]
30. Richy F, Dukas L, Schacht E. Differential effects of D-Hormone analogs and native vitamin D on the risk of falls: a comparative meta-analysis. Calcif Tissue Int 2008; 82: 102–7.
31. Ito S, Harada A, Kasai T et al. Use of alfacalcidol in osteoporotic patients with low muscle mass might increase muscle mass: an investigation using a patient database. Geriatr Gerontol Int 2014; 14: 122–8.
32. Hamdy NA, Kanis JA, Beneton MN et al. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ 1995; 310 (6976): 358–63.
33. Schact E, Richy F. Reduction of Falls in Elderly. The central role of Alfacalcidol in a multi-dimensional paradigm. Internet J Epidemiol 2008. http://ispub.com/IJE/7/1/5839
34. Dobnig H, Pilz S, Scharnagl H et al. Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality. Arch Intern Med 2008; 168 (12): 1340–9. http://archinte.jamanetwork.com/
35. Ярмолинская М.И. Постменопаузальный остеопороз: клиника, диагностика, профилактика, лечение. СПб., 2014; с. 30–5. / Iarmolinskaia M.I. Postmenopauzal'nyi osteoporoz: klinika, diagnostika, profilaktika, lechenie. SPb., 2014; s. 30–5. [in Russian]
36. Rang HP, Dale MM, Ritter JM. Rang and Dale's Pharmacology. 6th Revised edition 2007.
37. Бердникова Н.Г. Клиническая фармакология лекарственных средств, применяющихся при остеопорозе. Глава 33. Клиническая фармакология и фармакотерапия: учебник. Под ред. В.Г.Кукеса, А.К.Стародубцева. 3-е изд., доп. и перераб. М.: ГЭОТАР-Медиа, 2011. / Berdnikova N.G. Klinicheskaia farmakologiia lekarstvennykh sredstv, primeniaiushchikhsia pri osteoporoze. Glava 33. Klinicheskaia farmakologiia i farmakoterapiia: uchebnik. Pod red. V.G.Kukesa, A.K.Starodubtseva. 3-e izd., dop. i pererab. M.: GEOTAR-Media, 2011. [in Russian]
38. Heller HJ. The role of calcium in the prevention of kidney stones. J Am Coll Nutr 1999; 18 (5 Suppl.): 373S–378S.
39. Hall WD, Pettinger M, Oberman A et al. Risk factors for kidney stones in older women in the southern United States. Am J Med Sci 2001; 322 (1): 12–8.
40. Curban GC, Willett WC, Rimm EB et al. A prospective study of dietary calcium and other nutrients and risk symptomatic kidney stones. N Engl J Med 1993; 328: 833–8.
41. Генетический паспорт – основа индивидуальной и предиктивной медицины. Под ред. В.С.Баранова. СПб., 2009; с. 527. / Geneticheskii pasport – osnova individual'noi i prediktivnoi meditsiny. Pod red. V.S.Baranova. SPb., 2009; s. 527. [in Russian]
42. Mohammadi Z, Fayyazbakhsh F, Ebrahimi M et al. Association between vitamin D receptor gene polymorphisms (Fok1 and Bsm1) and osteoporosis: a systematic review. J Diabetes Metab Disord 2014; 13: 98.
43. Xu C, Tang P, Ding C et al. Vitamin D Receptor Gene FOKI Polymorphism Contributes to Increasing the Risk of HIV-Negative Tuberculosis: Evidence from a Meta-Analysis. PLoS One. Doi:10.1371/journal.pone.0140634 October 20, 2015.
44. Sei Won Kim, Jong Min Lee, Jick Hwan Ha et al. Association between vitamin D receptor polymorphisms and osteoporosis in patients with COPD. Int J COPD 2015; 10: 1809–17.
45. McCarty MF, DiNicolantonio JJ. The molecular biology and pathophysiology of vascular calcification. Postgrad Med 2014; 126 (2): 54–64.
46. Lewis JR, Radavelli-Bagatini S, Rejnmark et al. The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta-Analysis of Randomized Controlled Trials. J Bone Miner Res 2014. Doi: 10.1002/jbmr.2311.
________________________________________________
1. Fukumoto S, Martin TJ. Bone as an endocrine organ. Trends Endocrinol Metab 2009; 20 (5): 230–6.
2. Melent'eva A.A., Barysheva O.Iu., Vezikova N.N. i dr. Rol' faktora rosta fibroblastov 23 i faktora Klotho v razvitii mineral'no-kostnykh narushenii pri khronicheskoi bolezni pochek. Kurskii nauchno-prakt. vestn. “Chelovek i ego zdorov'e”. 2014; 3: 102–9. [in Russian]
3. Grebennikova T.A., Belaia Zh.E., Tsoriev T.T. i dr. Endokrinnaia funktsiia kostnoi tkani. Osteoporoz i osteopatii. 2015; 1: 28–37. [in Russian]
4. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266–81.
5. Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr 2004; 80 (6): 1706S–1709S.
6. Holick MF, Binkley NC et al. Weaver Evaluation, Treatment, and Prevention of Vitamin D. Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrin Metab 2011; 6: 1911–30
7. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab 2010; 95: 471–8.
8. Holick MF, Binkley NC, Heike A et al. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab 2012; 97 (4): 1153–8.
9. Klinicheskie rekomendatsii. Defitsit vitamina D u vzroslykh: diagnostika, lechenie i profilaktika. Rossiiskaia Assotsiatsiia Endokrinologov. FGBU “Endokrinologicheskii Nauchnyi Tsentr Ministerstva zdravookhraneniia RF”. M., 2015 http://www.endocrincentr.ru/images/material-images/Rek_Vit%20D_2015.pdf [in Russian]
10. IARC Working Group on Vitamin D: Vitamin D and Cancer. Report number 5. Geneva, Switzerland, WHO Press, 2008.
11. Peterlik M, Boonen St, Cross HS, Lamberg-Allardt C. Vitamin D and Calcium Insufficiency – Related Chronic Diseases: an Emerging World-Wide Public Health Problem. J Environ Res Public Health 2009; 6 (10): 2585–607. http://dx.doi.org/10.3390/ijerph6102585
12. Grant WB, Mohr SF. Ecological studies of ultraviolet B, vitamin D and cancer since 2000. Ann Epidemiol 2009; 19: 446–54.
13. Lappe JM, Travers-Gustafson D, Davies KM et al. And calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85 (6): 1586–91.
14. Kendrick J, Targher G, Smits G, Chonchol M. 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Exam Surv Atheroscler 2009; 205 (1): 255–60.
15. Egshatian L.V., Dudinskaia E.N., Tkacheva O.N., Kashtanova D.A. Rol' vitamina D v patogeneze khronicheskikh neinfektsionnykh zabolevanii. Osteoporoz i osteopatii. 2014; 1: 27–30. [in Russian]
16. Li C, Qiao G, Uskokovic M et al. Vitamin D: a negative endocrine regulator of the reninangiotensin system and blood pressure. J of Steroid Bioch and Molec Biol 2004; 89–90 (1–5): 387–92.
17. Afzal S, Nordestgaard BG. Low vitamin D and hypertension: a causal association? 2014. www.thelancet.com/diabetes-endocrinology. http://dx.doi.org/10.1016/S2213-8587(14)70119-6
18. Konradsen S, Ag H, Lindberg F et al. Serum 1.25-dihydroxy vitamin D is inversely associated with body mass index. Eur J Nutr 2008; 47 (2): 87–91.
19. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 2004; 27: 2813–8.
20. Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004; 79 (5): 820–5.
21. Harinarayan ChV. Vitamin D and diabetes mellitus. Hormones 2014; 13 (2): 163–81.
22. Vel'kov V.V. S-reaktivnyi belok – v laboratornoi diagnostike ostrykh vospalenii i v otsenke riskov sosudistykh patologii. Kliniko-laboratornyi konsilium. 2008; 2 (21): 37–48. [in Russian]
23. Liu PT, Stenger S, Li H et al. Vitamin D3-Triggered Antimicrobial Response – Another Pleiotropic Effect beyond Mineral and Bone Metabolism. Science 2006; 311: 1770–3.
24. Chun RF, Liu NQ, Lee T et al. Vitamin D supplementation and antibacterial immune responses in adolescents and young adults with HIV/AIDS. J Steroid Biochem Mol Biol 2014; 8: 148. http://dx.doi.org/10.1016/j.jsbmb.2014.07.013
25. Skaaby T, Nystrup Husemoen LL, Thuesen BH. Vitamin D Status and Chronic Obstructive Pulmonary Disease: A Prospective General Population Study. 2014; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0090654
26. Malinovschi А, Masoero М, Bellocchia М. Severe vitamin D deficiency is associated with frequent exacerbations and hospitalization in COPD patients. http://respiratory-research.com/content/15/1/131
27. Ringe JD et al. Alfacalcidol versus plain vitamin D in the treatment of glucocorticoid/inflammation-induced osteoporosis. J Rheumatol Suppl. 2005; 76: 33–40.
28. Ringe JD, Farahmand P, Schacht E. Alfacalcidol in men with osteoporosis: a prospective, observational, 2-year trial on 214 patients. Rheumatol Int 2013; 33 (3): 637–43.
29. Skripnikova I.A. Predotvrashchenie padenii – odin iz sposobov profilaktiki perelomov, sviazannykh s osteoporozom. Consilium Medicum. Neurology and Rheumatology (Suppl.). 2014; 16 (2): 66–70. [in Russian]
30. Richy F, Dukas L, Schacht E. Differential effects of D-Hormone analogs and native vitamin D on the risk of falls: a comparative meta-analysis. Calcif Tissue Int 2008; 82: 102–7.
31. Ito S, Harada A, Kasai T et al. Use of alfacalcidol in osteoporotic patients with low muscle mass might increase muscle mass: an investigation using a patient database. Geriatr Gerontol Int 2014; 14: 122–8.
32. Hamdy NA, Kanis JA, Beneton MN et al. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ 1995; 310 (6976): 358–63.
33. Schact E, Richy F. Reduction of Falls in Elderly. The central role of Alfacalcidol in a multi-dimensional paradigm. Internet J Epidemiol 2008. http://ispub.com/IJE/7/1/5839
34. Dobnig H, Pilz S, Scharnagl H et al. Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality. Arch Intern Med 2008; 168 (12): 1340-9. http://archinte.jamanetwork.com/
35. Iarmolinskaia M.I. Postmenopauzal'nyi osteoporoz: klinika, diagnostika, profilaktika, lechenie. SPb., 2014; s. 30–5. [in Russian]
36. Rang HP, Dale MM, Ritter JM. Rang and Dale's Pharmacology. 6th Revised edition 2007.
37. Berdnikova N.G. Klinicheskaia farmakologiia lekarstvennykh sredstv, primeniaiushchikhsia pri osteoporoze. Glava 33. Klinicheskaia farmakologiia i farmakoterapiia: uchebnik. Pod red. V.G.Kukesa, A.K.Starodubtseva. 3-e izd., dop. i pererab. M.: GEOTAR-Media, 2011. [in Russian]
38. Heller HJ. The role of calcium in the prevention of kidney stones. J Am Coll Nutr 1999; 18 (5 Suppl.): 373S–378S.
39. Hall WD, Pettinger M, Oberman A et al. Risk factors for kidney stones in older women in the southern United States. Am J Med Sci 2001; 322 (1): 12–8.
40. Curban GC, Willett WC, Rimm EB et al. A prospective study of dietary calcium and other nutrients and risk symptomatic kidney stones. N Engl J Med 1993; 328: 833–8.
41. Geneticheskii pasport – osnova individual'noi i prediktivnoi meditsiny. Pod red. V.S.Baranova. SPb., 2009; s. 527. [in Russian]
42. Mohammadi Z, Fayyazbakhsh F, Ebrahimi M et al. Association between vitamin D receptor gene polymorphisms (Fok1 and Bsm1) and osteoporosis: a systematic review. J Diabetes Metab Disord 2014; 13: 98.
43. Xu C, Tang P, Ding C et al. Vitamin D Receptor Gene FOKI Polymorphism Contributes to Increasing the Risk of HIV-Negative Tuberculosis: Evidence from a Meta-Analysis. PLoS One. Doi:10.1371/journal.pone.0140634 October 20, 2015.
44. Sei Won Kim, Jong Min Lee, Jick Hwan Ha et al. Association between vitamin D receptor polymorphisms and osteoporosis in patients with COPD. Int J COPD 2015; 10: 1809–17.
45. McCarty MF, DiNicolantonio JJ. The molecular biology and pathophysiology of vascular calcification. Postgrad Med 2014; 126 (2): 54–64.
46. Lewis JR, Radavelli-Bagatini S, Rejnmark et al. The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta-Analysis of Randomized Controlled Trials. J Bone Miner Res 2014. Doi: 10.1002/jbmr.2311.
Авторы
О.Ю.Климова*1, Н.Г.Бердникова1,2, Р.Е.Казаков3
1 ГБОУ ВПО Первый Московский государственный медицинский университет им. И.М.Сеченова Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2;
2 ГБУЗ Городская клиническая больница №23 им. И.В.Давыдовского Департамента здравоохранения г. Москвы. 119027, Россия, Москва, ул. Яузская, д. 11;
3 ФГБУ Научный центр экспертизы средств медицинского применения Минздрава России. 127051, Россия, Москва, Петровский б-р, д. 8
*oklimova2009@gmail.com
________________________________________________
O.Yu.Klimova*1, N.G.Berdnikova1,2, R.E.Kazakov3
1 I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 2;
2 I.M.Davidovckiy City Clinical Hospital №23. 119027, Russian Federation, Moscow, ul. Iauzskaia, d. 11;
3 Scientific Center for Expertise of Pharmaceuticals for Medical Use of the Ministry of Health of the Russian Federation. 127051, Russian Federation, Moscow, Petrovskii b-r, d. 8
*oklimova2009@gmail.com