title: Beta 1- and beta 2-antagonist activity of topically applied betaxolol and timolol in the systemic circulation.
abstract: The beta 1- and beta 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 microliters 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-beta 1-and beta 2-receptor occupancies corresponding drug plasma levels were calculated using radioligand binding techniques. The extent of beta 1-receptor occupancy of betaxolol in the systemic circulation was less than 20% and its beta 2-receptor occupancy was negligible. The extent of beta 1-receptor occupancy of timolol was about 65% and its beta 2-receptor occupancy about 80%. Because receptor occupancy is the basis of antagonist activity of beta-blocking agents, this study shows that the beta 1-antagonist activity of betaxolol in the systemic circulation is much less than that of timolol, and that its beta 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 beta 2-receptor blocking properties.
authors.affiliation: Department of Ophthalmology, University of Turku, Finland.
authors.forename: M L
authors.initials: ML
authors.lastname: Vuori
authors.forename: T
authors.initials: T
authors.lastname: Ali-Melkkilä
authors.forename: T
authors.initials: T
authors.lastname: Kaila
authors.forename: E
authors.initials: E
authors.lastname: Iisalo
authors.forename: K M
authors.initials: KM
authors.lastname: Saari
mesh_terms: D000287:Administration, Topical; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D015784:Betaxolol / Q000493:pharmacokinetics*; D006801:Humans; D008875:Middle Aged; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013999:Timolol / Q000493:pharmacokinetics*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551; D013999:Timolol; D015784:Betaxolol; C033394:CGP 12177