Clinical Pharmacokinetics

, Volume 12, Issue 5, pp 305–320 | Cite as

Clinical Pharmacokinetics of β-Adrenoceptor Antagonists

An Update
  • J. G. Riddell
  • D. W. G. Harron
  • R. G. Shanks
Review Article

Summary

The β-adrenoceptor antagonists have been widely used clinically for over 20 years and their pharmacokinetics have been more thoroughly investigated than any other group of drugs. Their various lipid solubilities are associated with differences in absorption, distribution and excretion. All are adequately absorbed, and some like atenolol, Sotalol and nadolol which are poorly lipid-soluble are excreted unchanged in the urine, accumulating in renal failure but cleared normally in liver disease. The more lipid-soluble drugs are subject to variable metabolism in the liver, which may be influenced by age, phenotype, environment, disease and other drugs, leading to more variable plasma concentrations. Their clearance is reduced in liver disease but is generally unchanged in renal dysfunction.

All the β-adrenoceptor antagonists reduce cardiac output and this may reduce hepatic clearance of highly extracted drugs. In addition, the metabolised drugs compete with other drugs for enzymatic biotransformation and the potential for interaction is great, but because of the high therapeutic index of β-adrenoceptor antagonists, any unexpected clinical effects are more likely to be due to changes in the kinetics of the other drug.

Because satisfactory plasma concentration effect relationships have been difficult to establish for most clinical indications, and little dose-related toxicity is seen, plasma β-adrenoceptor antagonist concentration measurement is usually unnecessary.

The investigation of the clinical pharmacokinetics of the β-adrenoceptor antagonists has added greatly to our theoretical and practical knowledge of pharmacokinetics and made some contribution to their better clinical use.

Keywords

Propranolol Metoprolol Atenolol Timolol Clinical Pharmacokinetic 

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Copyright information

© ADIS Press Limited 1987

Authors and Affiliations

  • J. G. Riddell
    • 1
  • D. W. G. Harron
    • 1
  • R. G. Shanks
    • 1
  1. 1.Department of Therapeutics and PharmacologyThe Queen’s University of BelfastBelfastNorthern Ireland

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