Plasma and aqueous humour concentrations and systemic effects of topical betaxolol and timolol in man

Abstract

Plasma and aqueous humour concentrations and systemic effects of timolol and betaxolol were studied after ocular administration in 45 patients scheduled for extracapsular cataract extraction and intraocular lens implantation. The patients were divided randomly into three groups and received 40 microliters of either 0.5% betaxolol, 0.25% timolol or placebo into the lower cul-de-sacs of both eyes. Blood samples were collected over a period of 4 h and blood pressure and heart rate were monitored during the study. Aqueous humour samples were aspirated at the beginning of the operation. Plasma and aqueous humour concentrations of timolol and betaxolol were analyzed using a sensitive radioreceptor assay. The mean plasma concentrations of betaxolol were lower than those of timolol. The concentration of betaxolol in the aqueous humour was twice as high as the concentration of timolol. Both drugs produced a significant decrease in heart rate. In the timolol group a decrease in heart rate was found 15 min after drug administration, and in the betaxolol group after one hour.

The effect of betaxolol and timolol on postoperative intraocular pressure

“…In this study betaxolol was significantly less effective than timolol five h postoperatively. In two previous studies (Vuori et al 1993;Vuori et al, unpublished) we measured the concentrations and receptor occupancies of betaxolol and timolol in aqueous humour. Betaxolol concentrations in the aqueous humour were 4100-330 ng/ml from one to five h and timolol 1650 ng/ml one h after instillation.…”

“…Ocular betaxolol hydrochloride was introduced as a I3,-selective antagonist (Berrospi & Leibowitz 1982), which might have fewer systemic side effect than topical timolol (McMahon et al 1979). Both drugs are rapidly absorbed into the systemic circulation and have systemic I3-blocking effects when administered topically (Kaila et al 1985;Vuori et al 1993).…”

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.…”

Pressure Lowering Medications

“…Smaller amount of 1 adrenoreceptors in the ocular tissue especially ciliary body as compared to 2 adrenoceptors is postulated to be the causative factor for lack of effectiveness of betaxolol. Topical instillation of betaxolol 0.5% results in plasma level of approximately 0.5ng/ml or half that of timolol 0.25% (Vuori et al, 1993). Betaxolol is the drug of choice in Early Manifest Glaucoma Trial (EMGT).…”