Pharmacokinetic Properties of the β-Adrenergic Receptor Blocking Drugs

Summary

The pharmacokinetic properties of the β-adrenergic receptor blocking drugs have been reviewed and discussed as a possible explanation for the wide range in therapeutic dose. As a general rule, the β-adrenergic receptor blocking action of these compounds is related, in a dose-dependent way, to their concentration in the circulation. The plasma concentrations of these drugs can vary widely after oral administration of the same dose in different individuals. This variation is especially great (up to 20-fold) for those drugs which have a high hepatic clearance (propranolol, alprenolol and oxprenolol), because a large and variable fraction of the drug is eliminated during the process of transfer of drug from the gut to the systemic circulation. Although half-life may be altered by route and duration of administration, it is always relatively short for propranolol, oxprenolol, alprenolol and pindolol (2 to 6 hours) necessitating a relatively short dosage interval. Practolol is unusual in that it is eliminated almost entirely by glomerular filtration and has a significantly longer half-life (9 to 12 hours). Although no data are available, it is likely to give less variable plasma concentrations.

It is concluded that individual variation in the disposition of these drugs can account, in part, for the wide range in effective dose; but that more information is required on the plasma concentrations associated with therapeutic benefit in the many and diverse conditions for which these drugs are indicated.