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.
Vuori
M L
ML
Department of Ophthalmology, University of Turku, Finland.
Kaila
T
T
Iisalo
E
E
Saari
K M
KM
D000042:Absorption; D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism*; D015784:Betaxolol / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D002387:Cataract Extraction; D006801:Humans; D007910:Lenses, Intraocular; D009883:Ophthalmic Solutions; D011412:Propanolamines / Q000378:metabolism; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D015784:Betaxolol; C033394:CGP 12177