Ocular and cardiac beta-antagonism by timolol prodrugs, timolol and levobunolol.

Topically applied O-butyryl timolol, O-pivaloyl timolol and levobunolol (0.25 micrograms) antagonized isoproterenol-induced ocular hypotension for 8 hrs whereas timolol (0.25 micrograms) was shorter acting (4 hrs). Timolol (25 micrograms) produced greater antagonism of isoproterenol-induced tachycardia than did O-butyryl and O-pivaloyl timolol (25 micrograms). These results suggest that, at similar doses, O-butyryl and O-pivaloyl timolol produce high concentrations of timolol in ocular tissues and undergo redistribution more slowly into the systemic circulation than does topical timolol. Under certain circumstances, prodrugs may provide a mechanism for increasing selectivity and extending the duration of action in the target organ as well as decreasing systemic effects.