ß 1 ‐ and ß 2 ‐antagonist activity of topically applied betaxolol and timolol in the systemic circulation

. The ß 1 ‐ and ß 2 ‐antagonist activity of betaxolol and timolol in the systemic circulation was studied ex‐vivo after their ocular administration in thirty patients during cataract surgery. The patients received 40 μl of 0.5% betaxolol or 0.25% timolol into the lower cul‐de‐sacs of both eyes. Blood samples were collected up to four h after instillation of the doses. Plasma concentrations of betaxolol and timolol were analyzed using a radioreceptor assay. The ex‐vivo‐ß 1 ‐and ß 2 ‐receptor occupancies corresponding drug plasma levels were calculated using radioligand binding techniques. The extent of ß 1 ‐receptor occupancy of betaxolol in the systemic circulation was less than 20% and its ß 2 ‐receptor occupancy was negligible. The extent of ß 1 ‐receptor occupancy of timolol was about 65% and its ß 2 ‐receptor occupancy about 80%. Because receptor occupancy is the basis of antagonist activity of ß‐blocking agents, this study shows that the ß 1 ‐antagonist activity of betaxolol in the systemic circulation is much less than that of timolol, and that its ß 2 ‐antagonist activity is negligible. The study suggests that the reported side effects of betaxolol in patients with obstructive pulmonary diseases are not mediated via its ß 2 ‐receptor blocking properties.