Pharmacokinetics and pharmacodynamics of β-blockers: in search of the optimal drug

June 28, 2023

β-blockers are a heterogeneous group of drugs in terms of their pharmacokinetic/pharmacodynamic parameters, which leads to clinically significant effects that must be taken into account in clinical practice. Analysis of the pharmacological characteristics of different representatives of this group allows us to consider bisoprolol as the optimal β-blockers due to a combination of promising pharmacokinetic properties. Clear linear pharmacokinetics, high cardio-selectivity and bioavailability, amphiphilicity and dual route of excretion, absence of presystemic metabolism, and independence of pharmacokinetics from genetic polymorphism of CYP2D6, CYP3A5, ADRB1 ensure minimal pharmacological variability of bisoprolol, which is the key to stability and reproducibility of clinical effects, high safety profile and minimal number of side effects.


  1. Zeppenfeld K., Tfelt-Hansen J., de Riva M. et al. (2022) 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur. Heart J., 43(40): 3997–4126. doi: 10.1093/eurheartj/ehac262.
  2. McDonagh T.A., Metra M., Adamo M. et al. (2021) 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J., 42(36): 3599–3726. doi: 10.1093/eurheartj/ehab368.
  3. Hindricks G., Potpara T., Dagres N. et al. (2021) 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur. Heart J., 42(5): 373–498.
  4. Knuuti J., Wijns W., Saraste A. et al. (2020) 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur. Heart J., 41(3): 407–477. doi: 10.1093/eurheartj/ehz425.
  5. Williams B., Mancia G., Spiering W. et al. (2018) 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur. Heart J., 39(33): 3021–3104. doi: 10.1093/eurheartj/ehy339.
  6. Tucker W.D., Sankar P., Kariyanna P.Th. (2023) Selective Beta-1 Blockers. In: StatPearls. Treasure Island (FL): StatPearls Publishing.
  7. Ladage D., Schwinger R.H., Brixius K. (2013) Cardio-selective beta-blocker: pharmacological evidence and their influence on exercise capacity. Cardiovasc. Ther., 31(2): 76–83. doi: 10.1111/j.1755-5922.2011.00306.x.
  8. AlHabeeb W., Mrabeti S., Abdelsalam A. (2022) Therapeutic Properties of Highly Selective β-blockers With or Without Additional Vasodilator Properties: Focus on Bisoprolol and Nebivolol in Patients With Cardiovascular Disease. Cardiovasc. Drugs Ther., 36(5): 959–971. doi: 10.1007/s10557-021-07205-y.
  10. Sykes D.A., Jiménez-Rosés M., Reilly J. (2022) Exploring the kinetic selectivity of drugs targeting the β1 -adrenoceptor. Pharmacol. Res. Perspect., 10(4): e00978. doi: 10.1002/prp2.978.
  11. Ågesen F.N., Weeke P.E., Tfelt-Hansen P. et al. (2019) Pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology. Pharmacol. Res. Perspect., 7(4): e00496. doi: 10.1002/prp2.496.
  12. Kumar N., Khan S.I., Versha F. et al. (2021) Comparison of Effect of Nebivolol and Bisoprolol on Sexual Function of Hypertensive Female Patients. Cureus, 13(5): e15062. doi: 10.7759/cureus.15062.
  13. Mustafaev I.I., Nurmamedova G.S. (2013) Effect of monotherapy with nebivolol, bisoprolol, carvedilol on the state of vegetative nervous system and sexual function in men with arterial hypertension. Kardiologiia, 53(2): 48–54.
  14. Maideen N.M.P., Rajkapoor B., Muthusamy S. et al. (2021) Review on Pharmacokinetic and Pharmacodynamic Drug Interactions of Adrenergic β-blockers with Clinically Relevant Drugs-An Overview. Curr. Drug Metab., 22(9): 672–682. doi: 10.2174/1389200222666210614112529.
  15. Collett S., Massmann A., Petry N. et al. (2023) JMetoprolol and CYP2D6: A Retrospective Cohort Study Evaluating Genotype-Based Outcomes. J. Pers. Med., 13(3): 416. doi: 10.3390/jpm13030416.
  16. Jung E., Ryu S., Park Z. et al. (2018) Influence of CYP2D6 Polymorphism on the Pharmacokinetic/Pharmacodynamic Characteristics of Carvedilol in Healthy Korean Volunteers. J. Korean Med. Sci., 33(27): e182. doi: 10.3346/jkms.2018.33.e182.
  17. Chan S.W., Chu T., Ho C. et al. (2021) Influence of CYP2D6 and CYP3A5 Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Bisoprolol in Hypertensive Chinese Patients. Front. Med. (Lausanne), 8: 683498. doi: 10.3389/fmed.2021.683498.
  18. Castaño-Amores C., Díaz-Villamarín X., Pérez-Gutiérrez A. et al. (2021) Pharmacogenetic polymorphisms affecting bisoprolol response. Biomed. Pharmacother., 142: 112069. doi: 10.1016/j.biopha.2021.112069.
  19. Momčilović S., Milovanović J., Janković S. et al. (2019) Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome. J. Cardiovasc. Pharmacol., 73(3): 136–142. doi: 10.1097/FJC.0000000000000644.
  20. Araújo Encinas J.F., Foncesca Peiró C. et al. (2021) Does nebivolol have renoprotective action in patients with chronic kidney disease conditions? An integrative review. Eur. J. Pharmacol., 905: 174180. doi: 10.1016/j.ejphar.2021.174180.
  21. Cvan Trobec K., Grabnar I., Kerec Kos M. et al. (2016) Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study. Eur. J. Clin. Pharmacol., 72(7): 813–822. doi: 10.1007/s00228-016-2041-1.
  22. Arita T., Suzuki S., Kato Y. et al. (2020) Association Between Dose and Plasma Concentration of Bisoprolol in Patients with Heart Failure (CVI ARO 6). Int. Heart J., 61(4): 748–754. doi: 10.1536/ihj.20-052.
  23. Momčilović S., Jovanović A., Radojković D. et al. (2020) Population pharmacokinetic analysis of bisoprolol in type 2 diabetic patients with hypertension. Eur. J. Clin. Pharmacol., 76(11): 1539–1546. doi: 10.1007/s00228-020-02937-6.
  24. Takayanagi R., Fujito K., Kimura K. et al. (2017) Analysis of Clinical Efficacy and Adverse Effects of β-Blocking Agents Used Clinically for Chronic Heart Failure. Biol. Pharm. Bull., 40(6): 837–843. doi: 10.1248/bpb.b16-00992.4