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Comparison of pharmacokinetic properties of beta-adrenoceptor blocking drugs

D. G. McDevitt
DOI: http://dx.doi.org/10.1093/eurheartj/8.suppl_M.9 9-14 First published online: 2 December 1987

Abstract

Beta-adrenoceptor blocking drugs can be characterised by their pharmacokinetic properties. One of the most important factors appears to be lipid solubility. Lipophilic beta-adrenoceptor antagonists, such as propranolol, oxprenolol and metoprolol, are cleared by the liver and undergo hepatic ‘first-pass’ metabolism. This results in low bioavailability, substantial interpatient variability in ‘steady-state’ plasma drug concentrations, rapid elimination half-lives and the possibility of drug interactions with other drugs such as pentobarbitone and cimetidine which affect hepatic enzymes. In addition, lipid soluble drugs are distributed widely within the body and penetrate the brain easily and rapidly. This may result in centrally mediated adverse effects such as vivid dreams.

In contrast, the more water-soluble beta-adrenoceptor blocking drugs, such as atenolol, sotalol and nadolol, are cleared by the kidney unchanged. They show less interpatient variation in plasma levels, have longer elimination half-lives and do not interact with drugs affecting hepatic enzymes. They penetrate the central nervous system less easily and cause less central side-effect.

Between these two extremes, there are several drugs like betaxolol, bisoprolol and pindolol, which are cleared partly by the liver and partly by the kidney. Their clearance is only altered by severe renal or hepatic disease, and they do not appear to interact with enzyme inducers or inhibitors.

  • Beta-adrenoceptor blocking drugs
  • lipid solubility
  • ‘first-pass’ effect
  • bioavailability
  • clearance