Skip to main content
SpringerLink
Log in

Pharmacokinetic Drug Interactions with Propranolol

  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Propranolol is widely used in clinical practice and is frequently administered along with other drugs. The co-administration of propranolol and other drugs may result in either propranolol-induced changes in the disposition of other drugs or in effects of the other drugs on the pharmacokinetics of propranolol. These changes may be due to alteration in absorption, metabolism or to haemodynamic effects such as altered liver blood flow.

Understanding the pharmacokinetics of propranolol is important to the rational interpretation of the effects of other drugs on propranolol’s disposition. The absorption, protein binding and metabolism of propranolol may all be affected by the co-administration of other drugs. Induction of propranolol’s metabolism by halofenate, phenytoin, phenobarbitone, rifampicin and alcohol have all been implicated in altering propranolol clearance, while inhibition of hepatic drug metabolising enzymes by chlorpromazine and cimetidine appear to reduce propranolol clearance.

Propranolol may also affect the metabolism of other drugs such as antipyrine, chlorpromazine, theophylline and thyroid hormones. Suggestions that propranolol may alter quinidine’s elimination have not been substantiated. By reducing liver blood flow propranolol may reduce the systemic clearance of other high extraction drugs such as lignocaine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bax, N.D.S.; Lennard, M.S. and Tucker, G.T.: Inhibition of antipyrine metabolism by β-adrenoreceptor antagonists. British Journal of Clinical Pharmacology 12: 779–784 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Branch, R.A.; Nies, A.S. and Shand, D.G.: General implications of the effects of liver blood flow on elimination from the perfused rat liver. Drug Metabolism and Disposition 1: 687–690 (1973).

    PubMed  CAS  Google Scholar 

  • Brown, J.E.; Kitchell, B.B.; Bjornsson, T.D. and Shand, D.G.: The artifactual nature of heparin-induced drug protein-binding alterations. Clinical Pharmacology and Therapeutics 30: 636–643 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Brunk, S.F.; Delle, M. and Wilson, W.R.: Effect of propranolol on morphine metabolism. Clinical Pharmacology and Therapeutics 16: 1039–1044 (1974).

    PubMed  CAS  Google Scholar 

  • Charles, B.G.; Renshaw, P.J.; Kay, J.J. and Ravenscroft, P.J.: Effect of metoclopramide on the bioavailability of long-acting propranolol. British Journal of Clinical Pharmacology II: 517–518 (1981).

    Article  Google Scholar 

  • Chiariello, M.; Volpe, M.; Rengo, F.; Trimarco, B.; Violini, R.; Ricciardelli, B. and Condorelli, M.: Effect of furosemide on plasma concentration and β-blockade by propranolol. Clinical Pharmacology and Therapeutics 26: 433–436 (1979).

    PubMed  CAS  Google Scholar 

  • Conrad, K.A. and Nyman, D.W.: Effects of metoprolol and propranolol on theophylline elimination. Clinical Pharmacology and Therapeutics 28: 463–467 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Cotham, R.H. and Shand, D.: Spuriously low plasma propranolol concentrations resulting from blood collection methods. Clinical Pharmacology and Therapeutics 18: 535–538 (1975).

    PubMed  CAS  Google Scholar 

  • Dobbs, J.; Skoutakis, V.A.; Acchiardo, S.R. and Dobbs, B.R.: Effects of aluminium hydroxide on the absorption of propranolol. Current Therapeutic Research 21: 887–892 (1977).

    CAS  Google Scholar 

  • Donovan, M.A.; Heagerty, A.M.; Patel, L.; Castleden, M. and Pohl, J.E.F.: Cimetidine and bioavailabilily of propranolol. Lancet I: 164 (1981).

    Article  Google Scholar 

  • Dorian, P.; Sellers, E.M.; Carruthers, G.; Hamilton, C. and Fan, T.: Propranolol-ethanol pharmacokinetic interaction. Clinical Pharmacology and Therapeutics 31: 219 (1982).

    Google Scholar 

  • Feely, J.; Wilkinson, G.R. and Wood, A.J.J.: Reduction ofliver blood flow and propranolol metabolism by cimetidine. New England Journal of Medicine 304: 692–695 (1981a).

    Article  PubMed  CAS  Google Scholar 

  • Feely, J.; Nakamura, K.; Branch, R.A.; Wilkinson, G.R. and Wood, A.J.J.: Increased clearance of propranolol due to furosemide. Clinical Research 29: 189A (1981b).

    Google Scholar 

  • Feely, J.; Isles, T.E.; Ratcliffe, W.A. and Crooks, J.: Propranolol, triiodothyronine, reverse triiodothyronine and thyroid disease. Clinical Endocrinology 10: 531–538 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Fenster, P.; Perrier, D.; Mayersohn, M. and Marcus, F.I.: Kinetic evaluation of the propranolol-quinidine combination. Clinical Pharmacology and Therapeutics 27: 450–453 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Grabowski, B.S.; Cady, W.J.; Young, W.W. and Emery, J.F.: Effects of acute alcohol administration on propranolol absorption. International Journal of Clinical Pharmacology, Therapy and Toxicology 18: 317–319 (1980).

    CAS  Google Scholar 

  • Greenblatt, D.J.; Franke, K. and Huffman, D.H.: Impairment of antipyrine clearance in humans by propranolol. Circulation 57: 1161–1164 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Heagerty, A.M.; Castleden, C.M. and Patel, L.: Failure of ranit-idine to interact with propranolol. British Medical Journal 284: 1304 (1982a).

    Article  PubMed  CAS  Google Scholar 

  • Heagerty, A.M.; Donovan, M.A.; Castleden, C.M.; Pohl, J.F. and Patel, L.: The influence of histamine (H2) antagonists on propranolol pharmacokinetics. International Journal of Clinical Pharmacology Research 2: 203–205 (1982b).

    CAS  Google Scholar 

  • Heagerty, A.M.; Donovan, M.A.; Castleden, C.M.; Pohl, J.F.; Patel, L. and Hedges, A.: Influence of cimetidine on pharmacokinetics of propranolol. British Medical Journal 282: 1917–1919 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Herman, R.J.; Nakamura, K.; Wilkinson, G.R. and Wood, A.J.J.: Induction of propranolol metabolism in man by rifampin. Pharmacologist 24: 181 (1982).

    Google Scholar 

  • Huffman, D.H.; Azarnoff, D.L.; Shoeman, D.W. and Dujovne, C.A.: The interaction between halofenate and propranolol. Clinical Pharmacology and Therapeutics 19: 807–812 (1976).

    PubMed  CAS  Google Scholar 

  • Kessler, K.M.; Humphries, W.CJr.; Black, M. and Spann, J.F.: Quinidine pharmacokinetics in patients with cirrhosis or receiving propranolol. American Heart Journal 96: 627–635 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Kirch, W.; Köholer, H.; Spahn, H. and Mutschier, E.: Interaction of cimetidine with metoprolol, propranolol, or atenolol. Lancet 2: 531–532 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Kornhauser, D.M.; Wood, A.J.J.; Vestal, R.E.; Wilkinson, G.R.; Branch, R.A. and Shand, D.G.: Biological determinants of propranolol disposition in man. Clinical Pharmacology and Therapeutics 23: 165–174 (1978).

    PubMed  CAS  Google Scholar 

  • McLean, A.J.; Skews, H.; Bobik, A. and Dudley, F.J.: Interaction between oral propranolol and hydralazine. Clinical Pharmacology and Therapeutics 27: 726–732 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Miller, F.A. and Rampling, D.: Adverse effects of combined propranolol and chlorpromazine therapy. American Journal of Psychiatry 139: 1198–1199 (1982).

    PubMed  CAS  Google Scholar 

  • Nics, A.S.; Evans, G.H. and Shand, D.G.: The hemodynamic effects of beta-adrenergic blockade on the flow dependent hepatic clearance of propranolol. Journal of Pharmacology and Experimental Therapeutics 184: 716–720 (1973).

    Google Scholar 

  • Ochs, H.R.; Greenblatt, D.J.; Woo, E.; Franke, K. and Smith, T.W.: Effect of propranolol on pharmacokinetics and acute electrocardiographic changes following intravenous quinidine in humans. Pharmacology 17: 301–306 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Ochs, H.R.; Carstens, G. and Greenblatt, D.J.: Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. New England Journal of Medicine 303: 373–377 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Pect, M.; Middlemiss, D.N. and Yates, R.A.: Pharmacokinetic interaction between propranolol and chlorpromazine in schizophrenic patients. Lancet 2: 978 (1980).

    Google Scholar 

  • Pessayre, D.; Lebrec, D.; Descatoire, V.; Peignoux, M. and Ben-hamou, J.P.: Mechanism for reduced drug clearance in patients with cirrhosis. Gastroenterology 74: 566–571 (1978).

    PubMed  CAS  Google Scholar 

  • Reed, W.E.; Tralbert, R.L. and Ludden, T.M.: Clearances of propranolol and quinidine. American Heart Journal 97: 678 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Reimann, I.W.; Klotz, U. and Frölich, J.C.: Cimetidine increased propranolol steady-state plasma levels in man. Eighth International Congress of Pharmacology, Tokyo, 0–57 (1981).

    Google Scholar 

  • Reimann, I.W.; Klotz, U. and Frölich, J.C.: Effects of cimetidine and ranitidine on steady-state propranolol kinetics and dynamics. Clinical Pharmacology and Therapeutics 32: 749–757 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Routledge, P.A. and Shand, D.G.: Clinical pharmacokinetics of propranolol. Clinical Pharmacokinetics 4: 73–90 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Shand, D.G.: Individualization of propranolol therapy. Medical Clinics of North America 58: 1063–1069 (1974).

    PubMed  CAS  Google Scholar 

  • Shand, D.G.; Branch, R.A.; Evans, G.H.; Nies, A.S. and Wilkinson, G.R.: The effects of saturable hepatic tissue uptake on drug clearance by the perfused rat liver. Drug Metabolism and Disposition 1: 679–686 (1973).

    PubMed  CAS  Google Scholar 

  • Shand, D.G. and Oates, J.A.: Metabolism of propranolol by rat liver microsomes and its inhibition by phenothiazine and tri-cyclic antidepressant drugs. Biochemical Pharmacology 20: 1720–1723 (1971).

    Article  CAS  Google Scholar 

  • Sotaniemi, E.A.; Anttila, M.; Pelkonen, R.O.; Järvensivu, P. and Sundquist, H.: Plasma clearance of propranolol and sotalol and hepatic drug-metabolizing enzyme activity. Clinical Pharmacology and Therapeutics 26: 153–161 (1979).

    PubMed  CAS  Google Scholar 

  • Sotaniemi, E.A.; Anttila, M.; Rautio, A.; Stengard, J.; Saukko, P. and Järvensivu P.: Propranolol and sotalol metabolism after a drinking party. Clinical Pharmacology and Therapeutics 29: 705–710 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Vestal, R.E.; Wood, A.J.J.; Branch, R.A.; Shand, D.G. and Wilkinson, G.R.: Effects of age and cigarette smoking on propranolol disposition. Clinical Pharmacology and Therapeutics 26: 8–15 (1979a).

    PubMed  CAS  Google Scholar 

  • Vestal, R.E.; Kornhauser, D.M.; Hollifield, J.W. and Shand, D.G.: Inhibition of propranolol metabolism by chlorpromazine. Clinical Pharmacology and Therapeutics 25: 19–24 (1979b).

    PubMed  CAS  Google Scholar 

  • Walle, T.; Conradi, E.C.; Walle, U.K.; Fagan, T.C. and Gaffney, T.E.: The predictable relationship between plasma levels and dose during chronic propranolol therapy. Clinical Pharmacology and Therapeutics 26: 668–677 (1978).

    Google Scholar 

  • Walle, T.; Conradi, E.C.; Walle, U.K.; Fagan, T.C. and Gaffney, T.E.: Propranolol glucuronide cumulation during long-term propranolol therapy: A proposed storage mechanism for propranolol. Clinical Pharmacology and Therapeutics 26: 686–695 (1979).

    PubMed  CAS  Google Scholar 

  • Walle, T.; Conradi, E.C.; Walle, U.K.; Fagan, T.C and Gaffney, T.E.: 4-Hydroxypropranolol and its glucuronide after single and long-term doses of propranolol. Clinical Pharmacology and Therapeutics 27: 22–31 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Warburton, S.; Opie, L.H.; Kennelley, B.M. and Müller, F.O.: Does cimetidine alter the cardiac response to exercise and propranolol? South African Medical Journal 55: 1124–1127 (1979).

    Google Scholar 

  • Wilkinson, G.R. and Shand, D.G.: A physiological approach to hepatic drug clearance. Clinical Pharmacology and Therapeutics 18: 377–390 (1975).

    PubMed  CAS  Google Scholar 

  • Wood, A.J.J.; Carr, K.; Vestal, R.E.; Belcher, S.; Wilkinson, G.R. and Shand, D.G.: Direct measurement of propranolol bio-availability during accumulation to steady-state. British Journal of Clinical Pharmacology 6: 345–350 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Wood, M.; Shand, D.G. and Wood, A.J.J.: Propranolol binding in plasma during cardiopulmonary bypass. Anesthesiology 51: 512–516 (1979a).

    Article  PubMed  CAS  Google Scholar 

  • Wood, M.; Shand, D. and Wood, A.J.J.: Altered drug binding due to the use of indwelling heparinized cannulas (heparin lock) for sampling. Clinical Pharmacology and Therapeutics 25: 103–107 (1979b).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Medicine and Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, USA

    Alastair J. J. Wood

  2. Department of Pharmacology and Therapeutics, University of Dundee, Ninewells Hospital, Dundee, UK

    John Feely

Authors
  1. Alastair J. J. Wood
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John Feely
    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

Wood, A.J.J., Feely, J. Pharmacokinetic Drug Interactions with Propranolol. Clin Pharmacokinet 8, 253–262 (1983). https://doi.org/10.2165/00003088-198308030-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198308030-00004

Keywords

Search

Navigation