Heart failure as a risk factor of adverse drug reactions. Part 1: potential changes in pharmacokinetics

The use of many drugs is associated with the risk of adverse drug reactions (ADRs), including those that increase mortality and / or morbidity and / or seek medical help or hospitalization, so called «drug-induced diseases» (DID). There is a number of factors that increase the risk of DID (risk factors) including comorbid diseases (for example, chronic kidney disease, hepatic impairment, obesity etc.). These pathologic conditions induce changes in pharmacokinetics (PK) and pharmacodynamics of drugs, thereby increasing the risk of ADRs. One of these diseases is heart failure (HF). Most studies of PK changes were conducted among patients with LVEF from 40 to 45 %, and excluded patients with concomitant diseases that could affect the PK of drugs (for example, serious liver and / or kidney diseases), therefore in polymorbid patients, trial findings may not be applicable. HF may be associated with a decrease in bioavailability, a decrease in volume of distribution, a change in the activity of cytochrome P450 isoenzymes, etc.
Individual dose and dosage regimen adjustment can significantly reduce risks, improve the quality of medical care and improve the prognosis in patients with heart failure.

1. Сычев Д. А., Остроумова О. Д., Кочетков А. И. и др. Лекарственно-индуцированные заболевания: эпидемиология и актуальность проблемы. Фарматека. 2020;27(5):77–84. [Sychev DA, Ostroumova OD, Kochetkov AI et al. Drug-induced diseases: epidemiology and urgency of the problem. Pharmateca. 2020;27(5):77–84. (In Russ).]. doi: 10.18565/pharmateca.2020.5.77-84

2. Tisdale JE, Miller DA. Drug Induced Diseases: Prevention, Detection, and Management. 3rd Ed. Bethesda, Md.: American Society of Health-System Pharmacists, 2018. 1399 р.

3. Сычев Д. А., Остроумова О. Д., Переверзев А. П., Кочетков А. И., Остроумова Т. М., Клепикова М. В., Эбзеева Е. Ю. Пожилой и старческий возраст пациентов как фактор риска развития лекарственно-индуцированных заболеваний. Безопасность и риск фармакотерапии. 2021;9(1):15–24. [Sychev DA, Ostroumova OD, Pereverzev AP, Kochetkov AI, Ostroumova TM, Klepikova MV, Ebzeeva EYu. Advanced age as a risk factor of drug-induced diseases. Bezopasnost’ i risk farmakoterapii = Safety and Risk of Pharmacotherapy. 2021;9(1):15–24. (In Russ).]. doi: 10.30895/2312-7821-2021-9-1-15-24

4. Lainscak M, Vitale C, Seferovic P et al. Pharmacokinetics and pharmacodynamics of cardiovascular drugs in chronic heart failure. Int J Cardiol. 2016;224:191–8. doi: 10.1016/j.ijcard.2016.09.015

5. Министерство здравоохранения Российской Федерации. Клинические рекомендации «Хроническая сердечная недостаточность». 2020. ID 156. [Ministry of Health of the Russian Federation. Clinical recommendations “Chronic heart failure”. 2020. ID 156. (In Russ).]. Доступно по: https://cr.minzdrav.gov.ru. Ссылка активна на 23.12.2021.

6. Dobre D, Borer JS, Fox K, et al. Heart rate: a prognostic factor and therapeutic target in chronic heart failure. The distinct roles of drugs with heart rate-lowering properties. Eur J Heart Fail. 2014;16(1):76–85. doi: 10.1093/eurjhf/hft129

7. Nicholls DP, Droogan A, Carson CA et al. Pharmacokinetics of flosequinan in patients with heart failure. Eur J Clin Pharmacol. 1996;50(4):289– 91. doi: 10.1007/s002280050110

8. Chu KM, Shieh SM, Hu OY. Pharmacokinetics and pharmacodynamics of enantiomers of pimobendan in patients with dilated cardiomyopathy and congestive heart failure after single and repeated oral dosing. Clin Pharmacol Ther. 1995;57(6):610–21. doi: 10.1016/0009-9236(95)90223-6

9. Brater DC. Pharmacokinetics of loop diuretics in congestive heart failure. Br Heart J. 1994;72(2 Suppl):S40–3. doi: 10.1136/hrt.72.2_suppl.s40

10. Farkas J, von Haehling S, Kalantar-Zadeh K et al. Cachexia as a major public health problem: frequent, costly, and deadly. J Cachexia Sarcopenia Muscle. 2013;4(3):173–8. doi: 10.1007/s13539-013-0105-y

11. Trobec K, Kos MK, von Haehling S et al. Pharmacokinetics of drugs in cachectic patients: a systematic review. PloS One. 2013;8(11):e79603. doi: 10.1371/journal.pone.0079603

12. Ogawa R, Stachnik JM, Echizen H. Clinical pharmacokinetics of drugs in patients with heart failure: an update (part 1, drugs administered intravenously). Clin Pharmacokinet. 2013;52(3):169–85. doi: 10.1007/s40262-012-0029-2

13. Benowitz NL, Meister W. Pharmacokinetics in patients with cardiac failure. Clin Pharmacokinet. 1976;1(6):389–405. doi: 10.2165/00003088-197601060-00001

14. Shammas FV, Dickstein K. Clinical pharmacokinetics in heart failure: an updated review. Clin Pharmacokinet. 1988;15(2):94–113. doi: 10.2165/00003088-198815020-00002

15. Ogawa R, Stachnik JM, Echizen H. Clinical pharmacokinetics of drugs in patients with heart failure: an update (part 2, drugs administered orally). Clin Pharmacokinet. 2014;53(12):1083–114. doi: 10.1007/s40262-014-0189-3

16. Mangoni AA, Jarmuzewska EA. The influence of heart failure on the pharmacokinetics of cardiovascular and non-cardiovascular drugs: a critical appraisal of the evidence. Br J Clin Pharmacol. 2019;85(1):20–36. doi: 10.1111/bcp.13760

17. Htet H, Saint NA, Lwin МA, Kyan А. Pharmacokinetic Changes in Congestive Heart Failure. JMSCR. 2017;05(07):24727–34. doi: 10.18535/jmscr/v5i7.71

18. Gottlieb SS, Khatta M, Wentworth D et al. The effects of diuresis on the pharmacokinetics of the loop diuretics furosemide and torsemide in patients with heart failure. Am J Med. 1998;104(6):533–8. doi: 10.1016/s0002-9343(98)00111-9

19. Kobayashi M, Fukumoto K, Ueno K. Effect of congestive heart failure on mexiletine pharmacokinetics in a Japanese population. Biol Pharm Bull. 2006;29(11):2267–9. doi: 10.1248/bpb.29.2267

20. Azzollini F, Cattò G, Iacuitti G et al. Ibopamine kinetics after a single oral dose in patients with congestive heart failure. Int J Clin Pharmacol Ther Toxicol. 1988;26(2):105–12.

21. Аляутдин Р. Н. Фармакология: учебник. 5-е изд., перераб. ГЭОТАР-Медиа, 2015. 1104 с. [Alyautdin RN. Farmakologiya: uchebnik. 5-e izd., pererab. GEOTAR-Media, 2015. (In Russ).].

22. Routledge PA, Shand DG. Presystemic drug elimination. Annu Rev Pharmacol Toxicol. 1979;19:447–68. doi: 10.1146/annurev.pa.19.040179.002311

23. Williams RL, Thakker KM, John V et al. Nitroglycerin absorption from transdermal systems: formulation effects and metabolite concentrations. Pharm Res. 1991;8(6):744–9. doi: 10.1023/a:1015802101272

24. Imhof PR, Vuillemin T, Gérardin A, et al. Studies of the bioavailability of nitroglycerin from a transdermal therapeutic system (Nitroderm TTS). Eur J Clin Pharmacol. 1984;27(1):7–12.

25. Sandek A, Bauditz J, Swidsinski A et al. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007;50(16):1561–9. doi: 10.1016/j.jacc.2007.07.016

26. Kishi T. Heart failure as an autonomic nervous system dysfunction. J Cardiol. 2012;59(2):117–22. doi: 10.1016/j.jjcc.2011.12.006

27. Huang X, Dorhout Mees E, Vos P et al. Everything we always wanted to know about furosemide but were afraid to ask. Am J Physiol Renal Physiol. 2016;310(10):F958–71. doi: 10.1152/ajprenal.00476.2015

28. Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413– 20. doi: 10.1023/a:1016212804288

29. Kim JS, Mitchell S, Kijek P et al. The suitability of an in situ perfusion model for permeability determinations: utility for BCS class I biowaiver requests. Mol Pharm. 2006;3(6):686–94. doi: 10.1021/mp060042f

30. Abdalrb GA, Mircioiu I, Amzoiu M et al. In Vitro and In Vivo Evaluation of Different Solid Dosage Forms Containing Captopril. Curr Health Sci J. 2017;43(3):214–9. doi: 10.12865/CHSJ.43.03.05

31. Charalabidis A, Sfouni M, Bergström C, Macheras P. The Biopharmaceutics Classification System (BCS) and the Biopharmaceutics Drug Disposition Classification System (BDDCS): Beyond guidelines. Int J Pharm. 2019;566:264–81. doi: 10.1016/j.ijpharm.2019.05.041

32. Brater DC, Day B, Burdette A, Anderson S. Bumetanide and furosemide in heart failure. Kidney Int. 1984;26(2):183–9. doi: 10.1038/ki.1984.153

33. Greither A, Goldman S, Edelen JS et al. Pharmacokinetics of furosemide in patients with congestive heart failure. Pharmacology. 1979;19(3):121–31. doi: 10.1159/000137299

34. Easthope SE, Jarvis B. Candesartan cilexetil: an update of its use in essential hypertension. Drugs. 2002;62(8):1253–87. doi: 10.2165/00003495-200262080-00016

35. van Lier JJ, van Heiningen PN, Sunzel M. Absorption, metabolism and excretion of 14C-candesartan and 14C-candesartan cilexetil in healthy volunteers. J Hum Hypertens. 1997;11 Suppl 2:S27–8.

36. Gadad AP, Reddy AD, Dandagi PM, Masthiholimath VS. Design and characterization of hollow/porous floating beads of captopril for pulsatile drug delivery. Asian Journal of Pharmaceutics. 2012;6(2):137–43. doi: 10.4103/0973-8398.102938

37. Kumar KM, Anil B. Biopharmaceutical disposition classification system: an extension of the bio pharmaceutical classification system. IRJP. 2012;3(3):5–10.

38. Yasir M, Asif M, Kumar A, Aggarval A. Biopharmaceutical classification system. International Journal of PharmaTech Research. 2010;2(3):1681–90.

39. Woosley RL, Echt DS, Roden DM. Effects of congestive heart failure on the pharmacokinetics and pharmacodynamics of antiarrhythmic agents. Am J Cardiol. 1986;57(3):25B–33B. doi: 10.1016/0002-9149(86)90995-1

40. Woosley RL. Pharmacokinetics and pharmacodynamics of antiarrhythmic agents in patients with congestive heart failure. Am Heart J. 1987;114(5):1280–91. doi: 10.1016/0002-8703(87)90217-1

41. Horiuchi I, Nozawa T, Fujii N et al. Pharmacokinetics of R- and S-Carvedilol in routinely treated Japanese patients with heart failure. Biol Pharm Bull. 2008;31(5):976–80. doi: 10.1248/bpb.31.976

42. Bellissant E, Giudicelli JF. Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients. Br J Clin Pharmacol. 2001;52(1):25–33. doi: 10.1046/j.0306-5251.2001.01410.x

43. Nies AS, Shand DG, Wilkinson GR. Altered hepatic blood flow and drug disposition. Clin Pharmacokinet. 1976;1(2):135–55. doi: 10.2165/00003088-197601020-00005