В статье обсуждаются вопросы фармакогенетики у пациентов с артериальной гипертензией, влияния фармакогенетического полиморфизма различных генов в эффективности и безопасности петлевого диуретика торасемида. Представлен обзор научных данных по влиянию генетического полиморфизма генов метаболизирующего фермента CYP2C9 и анионного транспортера на фармакокинетику препарата (печеночный и почечный клиренс), а также на фармакодинамику (выраженность диуретического и салуретического эффектов).
The article discusses the issues of pharmacogenetics in hypertensive patients, the influence of pharmacogenetic polymorphisms of different genes in the efficacy and safety of loop diuretic torasemide. A review of the scientific evidence on the influence of genetic polymorphism of metabolizing enzyme CYP2C9 and anion transporter on the pharmacokinetics of the drug (hepatic and renal clearance) and the pharmacodynamics (pronounced diuretic and salureticheskim effects) are also discussed.
1. Arnett DK, Claas SA, Glasser SP. Pharmacogenetics of antihypertensive treatment. Vascul Pharmacol 2006; 44 (2): 107–18.
2. Schelleman H, Stricker BH, De Boer A et al. Drug-gene interactions between genetic polymorphisms and antihypertensive therapy. Drugs 2004; 64 (16): 1801–16.
3. Polimanti R, Iorio A, Piacentini S et al. Human pharmacogenomic variation of antihypertensive drugs: from population genetics to personalized medicine. Pharmacogenomics 2014; 15 (2): 157–67.
4. Torrellas C, Carril JC, Cacabelos R. Benefits of Pharmacogenetics in the Management of Hypertension. J Pharmacogenomics Pharmacoproteomics 2014; 5: 1–7.
5. Collins R, Peto R, MacMahon S et al. Blood pressure, stroke, and coronary heart disease. Part 2: Short-term reductions in blood pressure: Overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827–38.
6. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338: b1665.
7. Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events. A systematic review. Stroke 2003; 34: 2741–9.
8. Psaty BM, Lumley T, Furberg CD et al. Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA 2003; 289: 2534–44.
9. Wright JM, Musini VM. First-line drugs for hypertension. Cohrane Database Syst Rev 2009; 8 (3): CD001841.
10. Xue H, Lu Z, Tang WL et al. First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. Cochrane Database Syst Rev.
11. Mancia G, Fagard R et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31: 1281–357.
12. Российское медицинское общество по артериальной гипертонии (РМОАГ), Всероссийское научное общество кардиологов (ВНОК). Диагностика и лечение артериальной гипертензии. Российские рекомендации (четвертый пересмотр), 2010. / Rossiiskoe meditsinskoe obshchestvo po arterial'noi gipertonii (RMOAG), Vserossiiskoe nauchnoe obshchestvo kardiologov (VNOK). Diagnostika i lechenie arterial'noi gipertenzii. Rossiiskie rekomendatsii (chetvertyi peresmotr), 2010. [in Russian]
13. Kent ST, Shimbo D, Huang L et al. Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007–2010. PLoS ONE 9 (8): e105888.
14. Baumgart P. Torasemide in comparison with thiazides in the treatment of hypertension. Cardiovasc Drugs Ther 1993; 7 (Suppl. 1): 63–8.
15. Friedel HA, Buckley MM. Torasemide. A review of its pharmacological properties and therapeutic potential. Drugs 1991; 41 (1): 81–103.
16. Dunn CJ, Fitton A, Brogden RN. Torasemide. An update of its pharmacological properties and therapeutic efficacy. Drugs 1995; 49: 121–42.
17. Uchida T, Yamanaga K, Nishikawa M et al. Anti-aldosteronergic effect of torasemide. Eur J Pharmacol 1991; 205: 145–50.
18. Baumgart P. Torasemide in comparison with thiazides in the treatment of hypertension. Cardiovasc.Drugs Ther 1993; 7 (Suppl. 1): 63–8.
19. Luft FC. Torasemide in the treatment of arterial hypertension. J Cardiovasc Pharmacol 1993; 22 (Suppl. 3): S32–S39.
20. Castañeda-Hernández G, Caillé G, du Souich P. Influence of drug formulation on drug concentration-effect relationships. Clin Pharmacokinet 1994; 26 (2): 135–43.
21. Spahn H, Knauf H, Mutschler E. Pharmacokinetics of torasemide and its metabolites in healthy controls and in chronic renal failure. Eur J Clin Pharmacol 1990; 39: 345–8.
22. Gehr TW, Rudy DW, Matzke GR et al. The pharmacokinetics of intravenous and oral torsemide in patients with chronic renal insufficiency. Clin Pharmacol Ther 1994; 56: 31–8.
23. Schwartz S, Brater DC, Pound D et al. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide in patients with cirrhosis. Clin Pharmacol Ther 1993; 54: 90–7.
24. Miners JO, Rees DL, Valente L et al. Human hepatic cytochrome P450 2C9 catalyzes the rate-limiting pathway of torsemide metabolism. J Pharmacol Exp Ther 1995; 272: 1076–81.
25. Miners JO, Coulter S, Birkett DJ et al. Torsemide metabolism by CYP2C9 variants and other human CYP2C subfamily enzymes. Pharmacogenetics 2000; 10: 267–70.
26. Lee CR, Goldstein JA, Pieper JA. Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics 2002; 12: 251–63.
27. Werner D, Werner U, Meybaum A et al. Determinants of steady-state torasemide pharmacokinetics: impact of pharmacogenetic factors, gender and angiotensin II receptor blockers. Clin Pharmacokinet 2008; 47 (5): 323–32.
28. Vormfelde SV, Schirmer M, Hagos Y et al. Torsemide renal clearance and genetic variation in luminal and basolateral organic anion transporters. Br J Clin Pharmacol 2006; 62 (3): 323–35.
29. Burckhardt G. Drug transport by Organic Anion Transporters (OATs). Pharmacol Ther 2012; 136 (1): 106–30.
30. Hasannejad H, Takeda M, Taki K et al. Interactions of human organic anion transporters with diuretics. J Pharmacol Exp Ther 2004; 308: 1021–9.
31. Vormfelde SV, Schirmer M, Hagos Y et al. Torsemide renal clearance and genetic variation in luminal and basolateral organic anion transporters. Br J Clin Pharmacol 2006; 62: 323–35.
32. Vormfelde SV, Toliat MR, Schirmer M et al. The polymorphisms Asn130Asp and Val174Ala in OATP1B1 and the CYP2C9 allele *3 independently affect torsemide pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2008; 83 (6): 815–7.
33. Vormfelde SV, Engelhardt S, Zirk A et al. CYP2C9 polymorphisms and the interindividual variability in pharmacokinetics and pharmacodynamics of the loop diuretic drug torsemide. Clin Pharmacol Ther 2004; 76: 557–66.
________________________________________________
1. Arnett DK, Claas SA, Glasser SP. Pharmacogenetics of antihypertensive treatment. Vascul Pharmacol 2006; 44 (2): 107–18.
2. Schelleman H, Stricker BH, De Boer A et al. Drug-gene interactions between genetic polymorphisms and antihypertensive therapy. Drugs 2004; 64 (16): 1801–16.
3. Polimanti R, Iorio A, Piacentini S et al. Human pharmacogenomic variation of antihypertensive drugs: from population genetics to personalized medicine. Pharmacogenomics 2014; 15 (2): 157–67.
4. Torrellas C, Carril JC, Cacabelos R. Benefits of Pharmacogenetics in the Management of Hypertension. J Pharmacogenomics Pharmacoproteomics 2014; 5: 1–7.
5. Collins R, Peto R, MacMahon S et al. Blood pressure, stroke, and coronary heart disease. Part 2: Short-term reductions in blood pressure: Overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827–38.
6. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338: b1665.
7. Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events. A systematic review. Stroke 2003; 34: 2741–9.
8. Psaty BM, Lumley T, Furberg CD et al. Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA 2003; 289: 2534–44.
9. Wright JM, Musini VM. First-line drugs for hypertension. Cohrane Database Syst Rev 2009; 8 (3): CD001841.
10. Xue H, Lu Z, Tang WL et al. First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. Cochrane Database Syst Rev.
11. Mancia G, Fagard R et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31: 1281–357.
12. Rossiiskoe meditsinskoe obshchestvo po arterial'noi gipertonii (RMOAG), Vserossiiskoe nauchnoe obshchestvo kardiologov (VNOK). Diagnostika i lechenie arterial'noi gipertenzii. Rossiiskie rekomendatsii (chetvertyi peresmotr), 2010. [in Russian]
13. Kent ST, Shimbo D, Huang L et al. Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007–2010. PLoS ONE 9 (8): e105888.
14. Baumgart P. Torasemide in comparison with thiazides in the treatment of hypertension. Cardiovasc Drugs Ther 1993; 7 (Suppl. 1): 63–8.
15. Friedel HA, Buckley MM. Torasemide. A review of its pharmacological properties and therapeutic potential. Drugs 1991; 41 (1): 81–103.
16. Dunn CJ, Fitton A, Brogden RN. Torasemide. An update of its pharmacological properties and therapeutic efficacy. Drugs 1995; 49: 121–42.
17. Uchida T, Yamanaga K, Nishikawa M et al. Anti-aldosteronergic effect of torasemide. Eur J Pharmacol 1991; 205: 145–50.
18. Baumgart P. Torasemide in comparison with thiazides in the treatment of hypertension. Cardiovasc.Drugs Ther 1993; 7 (Suppl. 1): 63–8.
19. Luft FC. Torasemide in the treatment of arterial hypertension. J Cardiovasc Pharmacol 1993; 22 (Suppl. 3): S32–S39.
20. Castañeda-Hernández G, Caillé G, du Souich P. Influence of drug formulation on drug concentration-effect relationships. Clin Pharmacokinet 1994; 26 (2): 135–43.
21. Spahn H, Knauf H, Mutschler E. Pharmacokinetics of torasemide and its metabolites in healthy controls and in chronic renal failure. Eur J Clin Pharmacol 1990; 39: 345–8.
22. Gehr TW, Rudy DW, Matzke GR et al. The pharmacokinetics of intravenous and oral torsemide in patients with chronic renal insufficiency. Clin Pharmacol Ther 1994; 56: 31–8.
23. Schwartz S, Brater DC, Pound D et al. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide in patients with cirrhosis. Clin Pharmacol Ther 1993; 54: 90–7.
24. Miners JO, Rees DL, Valente L et al. Human hepatic cytochrome P450 2C9 catalyzes the rate-limiting pathway of torsemide metabolism. J Pharmacol Exp Ther 1995; 272: 1076–81.
25. Miners JO, Coulter S, Birkett DJ et al. Torsemide metabolism by CYP2C9 variants and other human CYP2C subfamily enzymes. Pharmacogenetics 2000; 10: 267–70.
26. Lee CR, Goldstein JA, Pieper JA. Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics 2002; 12: 251–63.
27. Werner D, Werner U, Meybaum A et al. Determinants of steady-state torasemide pharmacokinetics: impact of pharmacogenetic factors, gender and angiotensin II receptor blockers. Clin Pharmacokinet 2008; 47 (5): 323–32.
28. Vormfelde SV, Schirmer M, Hagos Y et al. Torsemide renal clearance and genetic variation in luminal and basolateral organic anion transporters. Br J Clin Pharmacol 2006; 62 (3): 323–35.
29. Burckhardt G. Drug transport by Organic Anion Transporters (OATs). Pharmacol Ther 2012; 136 (1): 106–30.
30. Hasannejad H, Takeda M, Taki K et al. Interactions of human organic anion transporters with diuretics. J Pharmacol Exp Ther 2004; 308: 1021–9.
31. Vormfelde SV, Schirmer M, Hagos Y et al. Torsemide renal clearance and genetic variation in luminal and basolateral organic anion transporters. Br J Clin Pharmacol 2006; 62: 323–35.
32. Vormfelde SV, Toliat MR, Schirmer M et al. The polymorphisms Asn130Asp and Val174Ala in OATP1B1 and the CYP2C9 allele *3 independently affect torsemide pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2008; 83 (6): 815–7.
33. Vormfelde SV, Engelhardt S, Zirk A et al. CYP2C9 polymorphisms and the interindividual variability in pharmacokinetics and pharmacodynamics of the loop diuretic drug torsemide. Clin Pharmacol Ther 2004; 76: 557–66.
Авторы
М.В.Леонова*, Э.Э.Алимова, Ю.Н.Еремина
ФГБОУ ВО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1
*anti23@mail.ru
________________________________________________
M.V.Leonova*, E.E.Alimova, Yu.N.Eremina
N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1
*anti23@mail.ru