ß₁‐ and ß₂‐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.

Topical and systemic absorption in delivery of dexamethasone to the anterior and posterior segments of the eye

“…The posterior segment of the eye may receive drugs from topically applied eyedrops through either topical absorption into the eye or systemic absorption through the bloodstream (Saari et al. 1993; Vuori et al. 1993).…”

“…The pharmacokinetics and pharmacodynamics of the eye have been studied extensively Saari et al 1993;Urtti & Salminen 1993;Vuori et al 1993;Jarvinen et al 1995;Worakul & Robinson 1997;Raqhava et al 2004). With most formulations only a small fraction of an eyedrop dose will reach the posterior segment after topical administration (Urtti et al , 1990Acheampong et al 1995;Sigurdsson et al 2005).…”

“…However, the major proportion (50-95%) of the Topical and systemic absorption in delivery of dexamethasone to the anterior and posterior segments of the eye applied dose is absorbed systemically through the conjunctiva of the eye or via the nose (after the drug enters the lacrimal drainage system) (Jarvinen et al 1995). The posterior segment of the eye may receive drugs from topically applied eyedrops through either topical absorption into the eye or systemic absorption through the bloodstream Vuori et al 1993). We examined the relative roles of topical and systemic absorption in drug delivery to the retina and other ocular tissues.…”

Trimetazidine, a Metabolic Modulator, Has Cardiac and Extracardiac Benefits in Idiopathic Dilated Cardiomyopathy

“…23 The extent of ␤-blockade was estimated with a ␤1-adrenoceptor occupancy test. 24,25 Malondialdehyde concentration was measured as serum total (free and protein-bound) malondialdehyde as the 2,4-dinitrophenylhydrazine derivative by highperformance liquid chromatography with 1,1,3,3-tetraethoxypropane as the standard. 26 Human adipocyte fatty acid-binding protein was measured by a sandwich enzyme immunoassay (Human FABP4 ELISA, D-69120, Heidelberg, Germany).…”

Medications Used to Treat Glaucoma

“…75 These high aqueous concentrations of drug, even with the 0.25% dose, explain why betaxolol, which is highly selective for the beta-1 receptor, reaches a sufficient concentration to lower intraocular pressure, which is mediated through the beta-2 receptor. [76][77][78][79] Betaxolol lowers IOP 15-20%, but it does not lower pressure as much as the nonselective beta-blockers (20-25%). [80][81][82][83] All of the listed medications use benzalkonium chloride as the preservative, except Timoptic-XE and Timolol GFS, which use benzododecinium bromide 0.012% (also a quaternary ammonium compound) and Timolol Ocudose, which is supplied in preservative-free unit-dose 0.2 ml containers.…”