Skip to main content

Pharmacokinetic and Pharmacodynamic Properties of Metoprolol in Patients with Impaired Renal Function

Clinical Pharmacokinetics volume 5, pages 169–180 (1980)Cite this article

Summary

The pharmacokinetics of metoprolol have been studied in a group of patients with varying degrees of renal impairment and in healthy subjects after administration of 20mg of metoprolol tartrate intravenously and 50mg orally in a single dose and during steady-state conditions.

There were no significant differences in the extent of bioavailability or rate of elimination of the drug between the 2 groups. The fraction of the oral dose systemically available during steady-state was 59 ± 9% in the renal patients and 55 ± 7% in the control group. Total body clearance in the patients with renal failure was 1.0 ± 0.1L/min and in the healthy subjects it was 0.8 ± 0.1L/min. The corresponding values for the elimination half-life were 4.6 ± 1.2h and 4.1 ± 1.0h, respectively.

The β-adrenoceptor blocking effect of metoprolol (determined as percent reduction of exercise heart rate) did not differ significantly between the 2 groups during steady-state conditions. The effect on exercise heart rate was linearly related to the log of the plasma concentration of metoprolol. The relationship was identical for the single dose and during steady-state conditions, indicating that accumulation of metabolites in patients with renal failure does not influence the β-blocking properties of metoprolol.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

49,54 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  • Ablad, B.; Borg, K.O.; Carlsson, E.; Johnsson, G. and Regårdh, C.-G.: Metoprolol — a β-1 adrenoceptor antagonist; in Goldberg (Ed) Pharmacological and Biochemical Properties of Drug Substances, 2, 1979 (American Pharmaceutical Association, Washington 1979).

    Google Scholar 

  • Bengtsson, C.; Johnsson, G. and Regårdh, C.-G.: Plasma levels and effects of metoprolol on blood pressure and heart rate in hypertensive patients after an acute dose and between two doses during long term treatment. Clinical Pharmacology and Therapeutics 17: 400–408 (1975).

    PubMed  CAS  Google Scholar 

  • Bianchetti, G.; Graziani, G.; Brancaccio, D.; Morganti, A.; Leonetti, G.; Manfrin, M.; Sega, R.; Gomeni, R.; Ponticelli, C. and Morselli, P.L: Pharmacokinetics and effects of propranolol in terminal uraemic patients and in patients undergoing regular dialysis treatment. Clinical Pharmacokinetics 1: 373–384 (1976).

    PubMed  Article  CAS  Google Scholar 

  • Bodem, G.; Grieser, H.; Eichelbaum, M. and Gugler, R.: Pharmacokinetics of practolol in renal failure. European Journal of Clinical Pharmacology 7: 249–252 (1974).

    PubMed  Article  CAS  Google Scholar 

  • Borg, K.O.; Carlsson, E.; Hoffmann, K.-J.; Jönsson, T.-E.; Thorin, H. and Wallin, B.: Metabolism of metoprolol-(3H) in man, the dog and the rat. Acta Pharmacologica et Toxicologica 36(Suppl. V): 125–135 (1975).

    PubMed  CAS  Google Scholar 

  • Brogden, R.N.; Heel, R.C.; Speight, T.M. and Avery, G.S.: Metoprolol: A review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. Drugs 14: 321–348 (1977).

    PubMed  Article  CAS  Google Scholar 

  • Eastwood, J.B.; Curtis, J.R. and Smith, E.B.: Pharmacodynamics of practolol in chronic renal failure. British Medical Journal 4: 320–322 (1973).

    PubMed  Article  CAS  Google Scholar 

  • Ervik, M.; Hoffmann, K.-J. and Kylberg-Hansen, K.: Multiple ion monitoring of metoprolol and two metabolites in plasma and urine with deuterated internal standards. Biomedical Mass Spectrometry. In press (1980).

  • Gibaldi, M. and Perrier, D.: Pharmacokinetics, pp. 69, 151 (Marcel Dekker, New York 1975).

    Google Scholar 

  • Hill, L.F.: The pharmacokinetics of metoprolol in hypertensive patients with moderate renal failure; in Birdwood and Wink (Eds) Modern aspects of β-blocker therapy, p. 151–156 (Geigy Pharmaceuticals, Macclesfield 1978).

    Google Scholar 

  • Hoffmann, K.J.; Regårdh, C.-G.; Aurell, M.; Ervik, M. and Jordö, L.: The effect of impaired renal function on the plasma levels and urinary excretion of metoprolol metabolites. Clinical Pharmacokinetics 5: 181–191 (1980).

    PubMed  Article  CAS  Google Scholar 

  • Johansson, K.A.; Appelgren, C.; Borg, K.O. and Elofsson, R.: Binding of two adrenergic beta-receptor antagonists, alprenolol and H93/26 to human serum proteins. Acta Pharmaceutica Suecia 11: 333–346 (1974).

    CAS  Google Scholar 

  • Johnsson, G.; Regirdh, C.-G. and Sölvell, L.: Combined pharmacokinetic and pharmacodynamic studies in man on the adrenergic β1-receptor antagonist metoprolol. Acta Pharmacologica et Toxicologica 36(Suppl. V): 31–44 (1975).

    PubMed  CAS  Google Scholar 

  • Johnsson, G. and Regårdh, G.-G.: Clinical pharmacokinetics of β-adrenoceptor blocking drugs. Clinical Pharmacokinetics 1: 233–263 (1976).

    PubMed  Article  CAS  Google Scholar 

  • Jordö, L.; Johnsson, G.; Lundborg, P.; Persson, B.A.; Regårdh, C.-G. and Rönn, O.: Bioavailability and disposition of metoprolol and hydrochlorothiazide combined in one tablet and of separate doses of hydrochlorothiazide. British Journal of Clinical Pharmacology. 7: 563–567 (1979).

    PubMed  Article  Google Scholar 

  • Kaye, C.M.; Kumana, C.R.; Franklin, D.A. and Baker, L.R.I.: A study of practolol elimination in all grades of chronic renal failure. International Journal of Clinical Pharmacology 12: 83–88 (1975).

    CAS  Google Scholar 

  • Kendall, M.J.; Brown, D.; Grieve, A. and John, V.A.: Pharmacokinetic and pharmacodynamic studies of single oral doses of metoprolol in normal volunteers. European Journal of Drug Metabolism and Pharmacokinetics 2: 73–80 (1977).

    Article  CAS  Google Scholar 

  • Lavene, D.; Weiss, Y.A.; Safar, M.E.; Lovia, Y.; Agonis, N.; Georges, D. and Milliez, P.L: Pharmacokinetics and hepatic extraction ratio of pindolol in hypertensive patients with normal and impaired renal function. Journal of Clinical Pharmacology 17: 501–508 (1977).

    PubMed  CAS  Google Scholar 

  • Lowenthal, D.T.; Briggs, W.A.; Gibson, T.P.; Nelson, H. and Cirksena, W.J.: Pharmacokinetics of oral propranolol in chronic renal disease. Clinical Pharmacology and Therapeutics 16: 761–769 (1974).

    PubMed  CAS  Google Scholar 

  • Lowenthal, D.T.; Pitone, J.M.; Affrime, M.B.; Shirk, J.; Busby, P.; Kim, K.E.; Nancarrow, J.; Swartz, C.D. and Onesti, G.: Timolol kinetics in chronic renal insufficiency. Clinical Pharmacology and Therapeutics 23: 606–615 (1978).

    PubMed  CAS  Google Scholar 

  • Ohnhaus, E.E.; Nuesch, E.; Meier, J. and Kalberer, F.: Pharmacokinetics of uniabelled and 14C-labelled pindolol in uraemia. European Journal of Clinical Pharmacology 7: 25–29 (1974).

    PubMed  Article  CAS  Google Scholar 

  • Regårdh, C.-G.; Borg, K.O.; Johansson, R.; Johnsson, G. and Palmer, L.: Pharmacokinetic studies on the selective β1-receptor antagonist metoprolol in man. Journal of Pharmacokinetics and Biopharmaceutics 2: 347–364 (1974).

    PubMed  Google Scholar 

  • Regårdh, C.-G.; Johnsson, G.; Jordö, L. and Sölvell, L.: Comparative bioavailability and effect studies on metoprolol administered as ordinary and slow-release tablets in single and multiple doses. Acta Pharmacologics et Toxicologica 36(Suppl. V): 45–58 (1975).

    Google Scholar 

  • Regårdh, C.-G.: Pharmacokinetics and biopharmaceutics of some adrenergic beta-receptor antagonists with special emphasis on alprenolol and metoprolol. Acta Pharmacologica et Toxicologica 37(Suppl. 1): 1–39 (1975).

    PubMed  Google Scholar 

  • Sassard, J.; Pozet, N.; McAinsh, J.; Legheand, J. and Zech, P.: Pharmacokinetics of atenolol in patients with renal impairment. European Journal of Clinical Pharmacology 12: 175–180 (1977).

    PubMed  Article  CAS  Google Scholar 

  • Seiler, K.-J.; Schuster, K.J.; Meyer, G.-J.; Niedermeyer, W. and Wassermann, O.: The pharmacokinetics of metoprolol and its metabolites in dialysis patients. Clinical Pharmacokinetics 5: 192–198 (1980).

    PubMed  Article  CAS  Google Scholar 

  • Tjandramaga. T.B.; Thomas, J.; Verbeeck, R.; Verbesselt, R.; Verberckmoes, R. and De Schepper, P.J.: The effect of end-stage renal failure and hemodialysis on the elimination kinetics of Sotalol. British Journal of Clinical Pharmacology 3: 259–265 (1976).

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Departments of Medicine I and II, Sahlgren’s Hospital, Gothenburg and Research Laboratories, AB Hässle, Mölndal, Sweden

    L. Jordö, P. O. Attman, M. Aurell, L. Johansson, G. Johnsson &  Carl-Gunnar Regårdh

Authors
  1. L. Jordö
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. O. Attman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Aurell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Johansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Johnsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carl-Gunnar Regårdh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jordö, L., Attman, P.O., Aurell, M. et al. Pharmacokinetic and Pharmacodynamic Properties of Metoprolol in Patients with Impaired Renal Function. Clin Pharmacokinet 5, 169–180 (1980). https://doi.org/10.2165/00003088-198005020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198005020-00004

Keywords

  • Metoprolol
  • Impaired Renal Function
  • Timolol
  • Sotalol
  • Frusemide