Pharmacokinetics of long acting propranolol. Implications for therapeutic use.

Abstract

Beta-adrenoceptor antagonists are among the most commonly prescribed classes of drugs. They are indicated for the treatment of diseases such as hypertension and angina pectoris, in which long term therapy is often required. Since many beta-adrenoceptor antagonists have short plasma elimination half-lives, divided daily dosing has often been necessary in order to provide continuous beta-blockade throughout the day. However, such multiple-dose schedules may promote patient non-compliance and failure of the prescribed regimen. Long acting propranolol is a sustained release formulation of propranolol which has been developed to maintain therapeutic plasma propranolol concentrations throughout a 24-hour period while allowing once-daily dosing. Compared with conventionally formulated propranolol, long acting propranolol has a prolonged terminal half-life (8 to 11 hours), due to slower absorption from the gut. Systemic bioavailability of long acting propranolol is 30 to 50% less than that of the conventional formulation. This difference may result from increased hepatic metabolism. Peak drug concentrations are significantly lower than following identical doses of conventional propranolol, and the time to peak drug concentrations following administration is delayed. Relatively constant plasma concentrations and clinically significant inhibition of exercise-induced tachycardia are maintained throughout a 24-hour dosing interval following once-daily long acting propranolol. Once-daily long acting propranolol is as effective as divided doses of conventional propranolol for the treatment of hypertension and angina pectoris. Efficacy also appears comparable with once-daily administration of long acting conventional beta-adrenoceptor antagonists such as atenolol and nadolol. Once-daily long acting propranolol provides clinically significant sustained beta-adrenoceptor blockade and offers the potential for improved patient compliance due to once-daily dosing. Since provision of sustained beta-adrenoceptor blockade appears to be particularly important in the treatment of angina, this may be the principal indication for which long acting propranolol has a therapeutic advantage independent of its potential to improve compliance.