Plasma propranolol levels in beagle dogs after administration of propranolol hemisuccinate ester

The hemisuccinate ester of propranolol was administered to beagle dogs to test its applicability as a potential prodrug of propranolol. Following oral administration of propranolol hemisuccinate, plasma propranolol levels were eight times higher than after an equivalent dose of propranolol hydrochloride. The hemisuccinate was absorbed rapidly, with peak plasma levels observed at 0.5--1 hr. Following intravenous dosing, the disappearance half-life of the prodrug from the plasma was 0.5 hr while the propranolol half-life was 1.7 hr. This study demonstrated the potential usefulness of the prodrug approach when a highly metabolized drug such as propranolol is protected from first-pass elimination.