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Реальные и потенциальные преимущества антагониста кальция III поколения лерканидипина
Реальные и потенциальные преимущества антагониста кальция III поколения лерканидипина
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Аннотация
Рассмотрены особенности фармакокинетики дигидропиридинов III поколения (фармакокинетика, контролируемая мембраной). Сравнительные исследования показали наряду с большой продолжительностью действия высокую эффективность, не уступающую действию основных групп антигипертензивных препаратов. Для лерканидипина доказано нефропротективное действие, сопоставимое с таковым ингибиторов ангиотензинпревращающего фермента. Показана лучшая переносимость и безопасность в сравнении с антагонистами кальция II поколения.
Ключевые слова: артериальная гипертензия, амлодипин, лацидипин, лерканидипин, антагонисты кальция.
Key words: arterial hypertension, amplodipine, lacidipine, lercanidipine, calcium antagonists.
Ключевые слова: артериальная гипертензия, амлодипин, лацидипин, лерканидипин, антагонисты кальция.
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Key words: arterial hypertension, amplodipine, lacidipine, lercanidipine, calcium antagonists.
Полный текст
Список литературы
1. Leenen FHH. Clinical relevance of 24 hour blood pressure control by 1,4-dihydropyridines. Am J Hypertens 1996; 9: S97–S104.
2. Epstein M. Role of a third generation calcium antagonists in the management of hypertension. Drugs 1999; 57 (Suppl. 1): 1–10.
3. McClellan KJ, Jarvis B. Lercanidipine. A review of its use in hypertension. Drugs 2000; 60 (5): 1123–40.
4. Van Zweiten PA, Pfaffendorf M. Similarities and differences between calcium antagonists: Pharmacological aspects. J Hypertens 1993; 11 (Suppl. 1): S3–S11.
5. Van Zweiten PA, Pfaffendorf M. Pharmacology of dihydropyridine calcium antagonists; Relatiomship between lipophilicity and pharmacodynamic response. J Hypertens 1993; 11 (Suppl. 6): S3–S11.
6. Sranchez M, Sobrino J, Ribera L et al. Long-acting lacidipine versus short-acting nifedipine in the treatment of asymptomatic acute blood pressure increase. J Cardiovasc Pharmacol 1999; 33: 479–84.
7. Heber ME, Broadhurst PA, Bridgen GS et al. Effectiveness of the once-daily calcium antagonists, lacidipine, in controlling 24-hour ambulatory blood pressure. Am J Cardiol 1990; 66: 1228–32.
8. Gasser R, Koppel H, Klein W. Lercanidipine, a new third generation Ca-antagonist in the treatment of hypertension. J Clin Basic Cardiol 1999; 2: 169–74.
9. Leonardi A, Poggesi E, Tiiddei C et al. In vitro calcium antagonist activity of lercanidipine and its enantiomers. J Cardiovasc Pharmacol 1997; 29 (Suppl. 1): S10–S18.
10. Triggle DJ. Mechanisms of action of calcium channel antagonists. In: Calcium antagonists in clinical medicine. Ed. by M.Epstein. Philadelphia, 1998: pp. 1–26.
11. Nayler WG. Amlodipine. Berlin, 1995: p. 1–273.
12. Herbette LG, Vecchiarelli M, Leonardi A. Lercanidipine: Short plasma half-life, long duration of action. J Cardiovascul Pharmacol 1997; 29 (Suppl. 1): S19–S24.
13. Herbette LG, Gaviraghi G, Tulenko T et al. Molecular interaction between lacidipine and biological membranes. J Hypertens 1993; 11 (Suppl. 1): S13–S19.
14. Ahernethy DR, Schwartz JB. Calcium-antagonist drugs. N Engl J Med 1999; 341: 1447–57.
15. Specchia G, Saccaggi SP, Ghezzi C. Cardiovascular safety of lercanidipine in patients with angina pectoris: a review of six randomized clinical trials. Curr Ther Res 2001; 62: 3–15.
16. Angelico P, Guarneri L, Leonardi A et al. Vascular-selective effect of lercanidipine and other 1,4-dihydropyridines in isolated rabbit tissues. J Pharm Pharmacol 1999; 51: 709–14.
17. Policicchio D, Magliocca R, Malliani A. Efficacy and tolerability of lercanidipine in patients with mild to moderate essential hypertension: a comparative study with slow-release nifedipine. J Cardiovasc Pharmacol 1997; 29 (Suppl. 2): S31–5.
18. Leonetti G, Salvi S. A long-term study comparing lacidipine and nifedipine SR in hypertensive patients: safety data. J Cardiovasc Pharmacol 1994; 23 (Suppl. 5): S108–S110.
19. Lombardo D, Raimondi F. Efficacy and safety evaluation of lacidipine compared with amlodipine in mild-to-moderate hypertensive patients. J Cardiovasc Pharmacol 1994; 23 (Suppl. 5): S98–S100.
20. United Kingdom Lacidipine Study Group. A double-blind comparison of the efficacy and safety of lacidipine with atenolol in the treatment of essential hypertension. J Cardiovasc Pharmacol 1991; 17 (Suppl. 4): S27–S30.
21. Guedon J, Herrero G, Salvi S. Assessment of lacidipine, a new long-acting 1,4 dihydropyridine calcium antagonist, for the primary care of elderly hypertensive patients. Cardiol Eld 1993; 1: 141–8.
22. Romito R, Pansini MI, Perticone F et al. Comparative effect of lercandipine, felodipine and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercandipine in Adults (LEAD) study. J Clin Hypertens 2003; 5 (4): 249–53.
23. Cavallini A, Terzi G. Effects of antihypertensive therapy with lercanidipine and verapamil on cardiac electrical activity in patients with hypertension: a randomized, double-blind pilot study. Curr Ther Res 2000; 61 (7): 477–87.
24. Packer M, O'Connor M, Ghali JK et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med 1996; 335: 1107–14.
25. Barbagallo M, Barbagallo Sangiorgi G. Efficacy and tolerability of lercanidipine in monotherapy in elderly patients with isolated systolic hypertension. Aging Clin Exp Res 2000; 12 (5): 375–9.
26. Kizer IR, Kimmel SE. Epidemiologic review of calcium channel blocker drugs. Arch Intern Med 2001; 161: 1145–58.
27. Fogari R, Mugellini A, Corradi L et al. Efficacy of lercanidipine vs losartan on left ventricular hypertrophy in hypertensive type 2 diabetic patients [abstract no. P1.191]. J Hypertens 2000; 18 (Suppl. 2): S65.
28. S’anchez A, Sayans R, Alvarez JL et al. Left ventricular hypertrophy regression after a short antihypertensive treatment with lercanidipine vs. enalapril [abstract no. 12]. Fourth European Meeting on Calcium Antagonists, 1999, оct 27–29. Amsterdam.
29. Peterson JE, Adler S, Burkart LM et al. Blood pressure control, proteinuria and the progression of renal disease: the odification of diet in renal disease study. Ann Intern Med 1995; 123: 754–62.
30. Toto RD, Mitchell NC, Smith RO. «Strict» blood pressure control and progression of renal disease in hypertensive ephrosclerosis. Kidney Int 1995; 48: 851–9.
31. Gansevoort RT, Sluiter WJ, Hemrnelder MH et al. Antiproteinuric effect of blood pressure lowering agents: a metaanalysis of comparative trials. Nephrol Dial Transplant 1995; 10: 1963–74.
32. Pedrinelli R, Dell’Omo G, Nuti M et al. Heterogenous effect of calcium antagonists on leg oedema: a comparison of amlodipine versus lercanidipine in hypertensive patients. J Hypertens 2003; 21: 1969–73.
33. Cavallini A, Terzi G. Effects of antihypertensive therapy with lercanidipine and verapamil on cardiac electrical activity in patients with hypertension: a randomized, double-blind pilot study. Curr Ther Res 2000; 61 (7): 477–87.
34. Macchiarulo C, Pieri R, Mitolo DC et al. Antihypertensive effects of six calcium antagonists: evidence from Fourier analysis of 24-hour ambulatory blood pressure recordings. Curr Ther Res 2001; 62 (4): 236–53.
35. Fogari R, Malamani GD, Zoppi A et al. Comparative effect of lercanidipine and nifedipine gastrointestinal therapeutic system on ankle volume and subcutaneous interstitial pressure in hypertensive patients: a double-blind, randomized, parallel group study. Curr Ther Res Clin Exp 2000; 61: 850–62.
36. Paterna S, Licata A, Arnone S et al. Lercanidipine in two different dosage regimens as a sole treatment for severe essential hypertension. J Cardiovasc Pharmacol 1997; 29 (Suppl. 2): S50–3.
37. Barbagallo M, Barbagallo Sangiorgi G. Efficacy and tolerability of lercanidipine in monotherapy in elderly patients with isolated systolic hypertension. Aging Clin Exp Res 2000; 12 (5): 375–9.
38. Brown MJ, Palmer CR, Castaigne A et al. Morbidity and mortality in patients randomized to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the international nifedipine GITS study: intervention as a goal in hypertension treatment (INSIGHT). Lancet 2000; 356: 366–72.
39. Lewis E, Huncksicker LG, Clarke WR et al. Renoprotective effect of the angiotensinreceptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–60.
40. Parving III-I, Lehnert I-I, Brochner-Mortenscn I et al. For the study group Irbesartun in patients with type 2 diabetes and microalbumlnuria. N Engl J Med 2001; 345: 870–8.
41. Agodoa LY, Appel L, Bakris GL et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 2001; 285: 2719–28.
42. Epstein M. Calcium antagonists and renal protection: emerging perspectives. J Hypertens 1998; J8 (Suppl. 4): S17–25.
43. Sabbatini M, Leonardi A, Testa R et al. Effect of calcium antagonists on glomerular arterioles in spontaneously hypertensive rats. Hypertension 2000; 35: 775–9.
44. Bakris GL, Weir MR, DeQuattro V et al. The effects of an ACE inhibitor and a calcium antagonists on the progression of renal disease: the nephross study. Nephrol Dial Transplant 2001; J6: 2158–66.
45. Robles NR, Ocon J, Gomez CF et al. Лерканидипин у пациентов с хронической почечной недостаточностью: исследование ZAFRA. Кардиоваскулярная терапия и профилактика. 2010; 9 (4): 81–7.
46. Soma MR, Natali M, Donetti E et al. Effect of lercanidipine its (R)-enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits. Br J Pharmacol 1998; 125: 1471–6.
47. Lozano JV, Sanchis C, Llisterri JL. Efficacy of lercanidipine in poorly controlled hypertensive patients who follow a home blood pressure measurement training program [abstract no. R190]. J Hypertens 2002; 20 (Suppl. 4): S376.
48. Barrios V, Navarro A, Esteras A et al. Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE study. Blood Press 2002; 11 (2): 95–100.
49. Schwinger RHG, Schmidt-Mertens A. The new lipophillic calcium channel blocker lercanidipine combines high antihypertensive efficacy with low side effects [abstract no. P1–7]. Dtsch Med Wochenschr 2002; 127 (Suppl. 1): S13.
50. Romito R, Pansini MI, Perticone F et al. Comparative effect of lercanidipine, felodipine and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercandipine in Adults (LEAD) study. J Clin Hypertens 2003; 5 (4): 249–53.
51. Morisco C, Trimarco B. Efficacy and tolerability of lercanidipine in comparison to and in combination with atenolol in patients with mild to moderate hypertension in a double blind controlled study. J Cardiovasc Pharmacol 1997; 29 (Suppl. 2): S26–30.
52. Barbagallo M, Barbagallo Sangiorgi G. Efficacy and tolerability of lercanidipine in monotherapy in elderly patients with isolated systolic hypertension. Aging Clin Exp Res 2000; 12 (5): 375–9.
53. Acanfora D, Gheorgiade M, Rotiroti D et al. Acute dose-response, double-blind, placebo-controlled pilot study of Iercanidipine in patients with angina pectoris. Curr Ther Res 2000; 61: 255–65.
54. Leonetti G, Magnani B, Pessina AC et al. Tolerability of longterm treatment with lercanidipine versus amlodipine and lacidipine in elderly hypertensives. Am J Hypertens 2002; 15 (11): 932–40.
55. Borghi C, Prandin MG, Dormi A et al. Improved tolerability of the dihydropyridine calcium-channel antagonist lercanidipine: the lercanidipine challenge trial. Blood Press 2003; 12 (Suppl. 1): 1–8.
2. Epstein M. Role of a third generation calcium antagonists in the management of hypertension. Drugs 1999; 57 (Suppl. 1): 1–10.
3. McClellan KJ, Jarvis B. Lercanidipine. A review of its use in hypertension. Drugs 2000; 60 (5): 1123–40.
4. Van Zweiten PA, Pfaffendorf M. Similarities and differences between calcium antagonists: Pharmacological aspects. J Hypertens 1993; 11 (Suppl. 1): S3–S11.
5. Van Zweiten PA, Pfaffendorf M. Pharmacology of dihydropyridine calcium antagonists; Relatiomship between lipophilicity and pharmacodynamic response. J Hypertens 1993; 11 (Suppl. 6): S3–S11.
6. Sranchez M, Sobrino J, Ribera L et al. Long-acting lacidipine versus short-acting nifedipine in the treatment of asymptomatic acute blood pressure increase. J Cardiovasc Pharmacol 1999; 33: 479–84.
7. Heber ME, Broadhurst PA, Bridgen GS et al. Effectiveness of the once-daily calcium antagonists, lacidipine, in controlling 24-hour ambulatory blood pressure. Am J Cardiol 1990; 66: 1228–32.
8. Gasser R, Koppel H, Klein W. Lercanidipine, a new third generation Ca-antagonist in the treatment of hypertension. J Clin Basic Cardiol 1999; 2: 169–74.
9. Leonardi A, Poggesi E, Tiiddei C et al. In vitro calcium antagonist activity of lercanidipine and its enantiomers. J Cardiovasc Pharmacol 1997; 29 (Suppl. 1): S10–S18.
10. Triggle DJ. Mechanisms of action of calcium channel antagonists. In: Calcium antagonists in clinical medicine. Ed. by M.Epstein. Philadelphia, 1998: pp. 1–26.
11. Nayler WG. Amlodipine. Berlin, 1995: p. 1–273.
12. Herbette LG, Vecchiarelli M, Leonardi A. Lercanidipine: Short plasma half-life, long duration of action. J Cardiovascul Pharmacol 1997; 29 (Suppl. 1): S19–S24.
13. Herbette LG, Gaviraghi G, Tulenko T et al. Molecular interaction between lacidipine and biological membranes. J Hypertens 1993; 11 (Suppl. 1): S13–S19.
14. Ahernethy DR, Schwartz JB. Calcium-antagonist drugs. N Engl J Med 1999; 341: 1447–57.
15. Specchia G, Saccaggi SP, Ghezzi C. Cardiovascular safety of lercanidipine in patients with angina pectoris: a review of six randomized clinical trials. Curr Ther Res 2001; 62: 3–15.
16. Angelico P, Guarneri L, Leonardi A et al. Vascular-selective effect of lercanidipine and other 1,4-dihydropyridines in isolated rabbit tissues. J Pharm Pharmacol 1999; 51: 709–14.
17. Policicchio D, Magliocca R, Malliani A. Efficacy and tolerability of lercanidipine in patients with mild to moderate essential hypertension: a comparative study with slow-release nifedipine. J Cardiovasc Pharmacol 1997; 29 (Suppl. 2): S31–5.
18. Leonetti G, Salvi S. A long-term study comparing lacidipine and nifedipine SR in hypertensive patients: safety data. J Cardiovasc Pharmacol 1994; 23 (Suppl. 5): S108–S110.
19. Lombardo D, Raimondi F. Efficacy and safety evaluation of lacidipine compared with amlodipine in mild-to-moderate hypertensive patients. J Cardiovasc Pharmacol 1994; 23 (Suppl. 5): S98–S100.
20. United Kingdom Lacidipine Study Group. A double-blind comparison of the efficacy and safety of lacidipine with atenolol in the treatment of essential hypertension. J Cardiovasc Pharmacol 1991; 17 (Suppl. 4): S27–S30.
21. Guedon J, Herrero G, Salvi S. Assessment of lacidipine, a new long-acting 1,4 dihydropyridine calcium antagonist, for the primary care of elderly hypertensive patients. Cardiol Eld 1993; 1: 141–8.
22. Romito R, Pansini MI, Perticone F et al. Comparative effect of lercandipine, felodipine and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercandipine in Adults (LEAD) study. J Clin Hypertens 2003; 5 (4): 249–53.
23. Cavallini A, Terzi G. Effects of antihypertensive therapy with lercanidipine and verapamil on cardiac electrical activity in patients with hypertension: a randomized, double-blind pilot study. Curr Ther Res 2000; 61 (7): 477–87.
24. Packer M, O'Connor M, Ghali JK et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med 1996; 335: 1107–14.
25. Barbagallo M, Barbagallo Sangiorgi G. Efficacy and tolerability of lercanidipine in monotherapy in elderly patients with isolated systolic hypertension. Aging Clin Exp Res 2000; 12 (5): 375–9.
26. Kizer IR, Kimmel SE. Epidemiologic review of calcium channel blocker drugs. Arch Intern Med 2001; 161: 1145–58.
27. Fogari R, Mugellini A, Corradi L et al. Efficacy of lercanidipine vs losartan on left ventricular hypertrophy in hypertensive type 2 diabetic patients [abstract no. P1.191]. J Hypertens 2000; 18 (Suppl. 2): S65.
28. S’anchez A, Sayans R, Alvarez JL et al. Left ventricular hypertrophy regression after a short antihypertensive treatment with lercanidipine vs. enalapril [abstract no. 12]. Fourth European Meeting on Calcium Antagonists, 1999, оct 27–29. Amsterdam.
29. Peterson JE, Adler S, Burkart LM et al. Blood pressure control, proteinuria and the progression of renal disease: the odification of diet in renal disease study. Ann Intern Med 1995; 123: 754–62.
30. Toto RD, Mitchell NC, Smith RO. «Strict» blood pressure control and progression of renal disease in hypertensive ephrosclerosis. Kidney Int 1995; 48: 851–9.
31. Gansevoort RT, Sluiter WJ, Hemrnelder MH et al. Antiproteinuric effect of blood pressure lowering agents: a metaanalysis of comparative trials. Nephrol Dial Transplant 1995; 10: 1963–74.
32. Pedrinelli R, Dell’Omo G, Nuti M et al. Heterogenous effect of calcium antagonists on leg oedema: a comparison of amlodipine versus lercanidipine in hypertensive patients. J Hypertens 2003; 21: 1969–73.
33. Cavallini A, Terzi G. Effects of antihypertensive therapy with lercanidipine and verapamil on cardiac electrical activity in patients with hypertension: a randomized, double-blind pilot study. Curr Ther Res 2000; 61 (7): 477–87.
34. Macchiarulo C, Pieri R, Mitolo DC et al. Antihypertensive effects of six calcium antagonists: evidence from Fourier analysis of 24-hour ambulatory blood pressure recordings. Curr Ther Res 2001; 62 (4): 236–53.
35. Fogari R, Malamani GD, Zoppi A et al. Comparative effect of lercanidipine and nifedipine gastrointestinal therapeutic system on ankle volume and subcutaneous interstitial pressure in hypertensive patients: a double-blind, randomized, parallel group study. Curr Ther Res Clin Exp 2000; 61: 850–62.
36. Paterna S, Licata A, Arnone S et al. Lercanidipine in two different dosage regimens as a sole treatment for severe essential hypertension. J Cardiovasc Pharmacol 1997; 29 (Suppl. 2): S50–3.
37. Barbagallo M, Barbagallo Sangiorgi G. Efficacy and tolerability of lercanidipine in monotherapy in elderly patients with isolated systolic hypertension. Aging Clin Exp Res 2000; 12 (5): 375–9.
38. Brown MJ, Palmer CR, Castaigne A et al. Morbidity and mortality in patients randomized to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the international nifedipine GITS study: intervention as a goal in hypertension treatment (INSIGHT). Lancet 2000; 356: 366–72.
39. Lewis E, Huncksicker LG, Clarke WR et al. Renoprotective effect of the angiotensinreceptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–60.
40. Parving III-I, Lehnert I-I, Brochner-Mortenscn I et al. For the study group Irbesartun in patients with type 2 diabetes and microalbumlnuria. N Engl J Med 2001; 345: 870–8.
41. Agodoa LY, Appel L, Bakris GL et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 2001; 285: 2719–28.
42. Epstein M. Calcium antagonists and renal protection: emerging perspectives. J Hypertens 1998; J8 (Suppl. 4): S17–25.
43. Sabbatini M, Leonardi A, Testa R et al. Effect of calcium antagonists on glomerular arterioles in spontaneously hypertensive rats. Hypertension 2000; 35: 775–9.
44. Bakris GL, Weir MR, DeQuattro V et al. The effects of an ACE inhibitor and a calcium antagonists on the progression of renal disease: the nephross study. Nephrol Dial Transplant 2001; J6: 2158–66.
45. Robles NR, Ocon J, Gomez CF et al. Лерканидипин у пациентов с хронической почечной недостаточностью: исследование ZAFRA. Кардиоваскулярная терапия и профилактика. 2010; 9 (4): 81–7.
46. Soma MR, Natali M, Donetti E et al. Effect of lercanidipine its (R)-enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits. Br J Pharmacol 1998; 125: 1471–6.
47. Lozano JV, Sanchis C, Llisterri JL. Efficacy of lercanidipine in poorly controlled hypertensive patients who follow a home blood pressure measurement training program [abstract no. R190]. J Hypertens 2002; 20 (Suppl. 4): S376.
48. Barrios V, Navarro A, Esteras A et al. Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE study. Blood Press 2002; 11 (2): 95–100.
49. Schwinger RHG, Schmidt-Mertens A. The new lipophillic calcium channel blocker lercanidipine combines high antihypertensive efficacy with low side effects [abstract no. P1–7]. Dtsch Med Wochenschr 2002; 127 (Suppl. 1): S13.
50. Romito R, Pansini MI, Perticone F et al. Comparative effect of lercanidipine, felodipine and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercandipine in Adults (LEAD) study. J Clin Hypertens 2003; 5 (4): 249–53.
51. Morisco C, Trimarco B. Efficacy and tolerability of lercanidipine in comparison to and in combination with atenolol in patients with mild to moderate hypertension in a double blind controlled study. J Cardiovasc Pharmacol 1997; 29 (Suppl. 2): S26–30.
52. Barbagallo M, Barbagallo Sangiorgi G. Efficacy and tolerability of lercanidipine in monotherapy in elderly patients with isolated systolic hypertension. Aging Clin Exp Res 2000; 12 (5): 375–9.
53. Acanfora D, Gheorgiade M, Rotiroti D et al. Acute dose-response, double-blind, placebo-controlled pilot study of Iercanidipine in patients with angina pectoris. Curr Ther Res 2000; 61: 255–65.
54. Leonetti G, Magnani B, Pessina AC et al. Tolerability of longterm treatment with lercanidipine versus amlodipine and lacidipine in elderly hypertensives. Am J Hypertens 2002; 15 (11): 932–40.
55. Borghi C, Prandin MG, Dormi A et al. Improved tolerability of the dihydropyridine calcium-channel antagonist lercanidipine: the lercanidipine challenge trial. Blood Press 2003; 12 (Suppl. 1): 1–8.
Авторы
А.А.Кириченко
ГБОУ ДПО Российская медицинская академия последипломного образования, Москва
ГБОУ ДПО Российская медицинская академия последипломного образования, Москва
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