Pharmacodynamic models of various beta blockers: an explanation for the long duration of action of bopindolol

Abstract

Models describing the time course of effects (pharmacodynamic models) of various beta blockers in man are used to explain the long duration of action of bopindolol. No matter what effect is used [reduction in exercise heart rate (RER) or isoproterenol dose ratio (DR)] human data show clearly that bopindolol is very potent compared to other beta blockers such as atenolol, metoprolol, pindolol, practolol, and propranolol. In pharmacokinetic terms, however, these drugs show no pronounced difference in their elimination half-life (ranging between 4 and 8 h). Also the site of action of the therapeutic effects (beta 1 receptors) is obviously identical for all beta blockers. Furthermore, there is no evidence to suggest that bopindolol (the prodrug) or hydrolyzed bopindolol (the active substance) is further metabolized to a slowly eliminated active metabolite. Thus, drug disposition provides no argument to explain the long-lasting effects of bopindolol as compared other beta blockers. The long duration of action of bopindolol seems to reflect an usually flat plasma concentration-response curve.