Concentrations and antagonist activity of topically applied betaxolol in aqueous humour

Aqueous humour concentrations and antagonist activity of betaxolol were studied after ocular administration in forty-five patients scheduled for cataract surgery. The patients were randomly divided into five groups and received 40 microliters of 0.5% betaxolol into the lower cul-de-sac of one eye. In groups I, II, III and IV the drug was instilled 5-6, 12, 24 and 48 h, respectively, before surgery, into the eye to be operated, and in group V 4 h before surgery into the contralateral eye. Aqueous humour samples were aspirated at the beginning of the operation. Aqueous humour concentrations of betaxolol were analyzed using a radioreceptor assay, and the ex-vivo-beta 1- and beta 2-receptor occupancies of betaxolol were calculated. The highest concentration of betaxolol in aqueous humour was found 5-6 hours after instillation of the drug. Topical betaxolol was found to stay in aqueous humour for 48 h, a much longer time than the recommended interval of dosage. Betaxolol beta 1-receptor occupancy was 99-95% during the study, but also beta 2-receptor occupancy was significant (52%) 24 h after instillation of the drug. Because receptor occupancy is the basis of antagonist activity, the role of beta 2-receptor blocking effect of betaxolol in lowering intraocular pressure cannot be excluded.