Ocular Levobunolol

Abstract

Levobunolol¹ is a potent non-selective β-adrenoceptor blocking agent used for the topical treatment of increased intraocular pressure in patients with chronic open angle glaucoma or ocular hypertension. In comparative studies of up to 2 years’ duration levobunolol 0.5 to 1% reduced intraocular pressures by about 30% and adequately controlled intraocular hypertension in 50 to 85% of those treated. These results were significantly superior to those produced by placebo and comparable to the responses achieved with ocular timolol in double-blind controlled trials. Levobunolol has been well tolerated, producing only minor changes in objective and subjective ophthalmic and systemic parameters. Adverse reactions resulted in approximately 5% of patients withdrawing from treatment with levobunolol which was equivalent to that observed with timolol. Thus, ocular levobunolol is a well-tolerated and effective therapy for the management of raised intraocular pressure, and is a suitable alternative to ocular timolol in patients with chronic open angle glaucoma or ocular hypertension. Following ocular administration, levobunolol produced a dose-related reduction of intraocular pressure in healthy volunteers and in patients with open angle glaucoma or ocular hypertension. The maximum effect on intraocular pressure was produced by levobunolol 1% with peak effects occurring between 2 and 6 hours after application and intraocular pressure reductions lasting for at least 12 hours. In comparative studies in patients with open angle glaucoma or ocular hypertension levobunolol 0.5 to 1% and timolol 0.5% produced comparable reductions in intraocular pressure. The mechanism of the ocular antihypertensive effects of levobunolol is unclear but, as for timolol, is probably related to suppression of aqueous humour formation. Haemodynamic changes following topical levobunolol administration have included small statistically insignificant decreases in heart rate and blood pressure which were assessed to have little clinical importance. There is only limited information available on the pharmacokinetic properties of levobunolol after ocular administration in humans. Further studies are needed to determine the extent of systemic absorption. In rabbits, following topical application of single doses of radio-labelled racemic bunolol, radioactivity was detected in anterior ocular tissues with highest concentrations in cornea and iris and peak levels detected 30 minutes after administration. Levobunolol is rapidly absorbed after oral administration to healthy subjects, mean peak plasma concentrations usually occurring between 1 and 3 hours after administration. The apparent volume of distribution of levobunolol was 5.5 L/kg after an intravenous dose of 8mg. Following oral administration, 3 and 78% of the dose appeared in faeces and urine, respectively, primarily as the main metabolite dihydrolevobunolol. The elimination half-life of levobunolol in humans appears to be approximately 6 hours and its total plasma clearance 0.66 L/h. Levobunolol has been compared with placebo and timolol in double-masked trials of up to 2 years duration in patients with chronic open angle glaucoma or ocular hypertension. In a 3-month double-blind study levobunolol 0.5 and 1% produced a mean reduction in intraocular pressure of 30% compared with a 2% reduction produced by placebo. Furthermore, in both short and long term comparative studies levobunolol 0.25 to 1% decreased intraocular pressure by 18 to 32% from baseline, and this was not statistically different from pressure reductions (17 to 31%) produced by timolol 0.125 to 5%. In addition, there was no statistically significant difference between levobunolol and timolol in the percentage of patients who achieved satisfactory intraocular pressure control. The effects of levobunolol were sustained over long periods with no evidence of drifting of intraocular pressure or tolerance. In general, topical administration of levobunolol (0.25 to 1%) has been well tolerated in studies of up to 2 years duration. Adverse reactions resulted in approximately 5% of patients withdrawing from levobunolol treatment which was equivalent to that observed with timolol. The most significant adverse reactions were blepharitis, conjunctivitis, decreased visual acuity, superficial punctate keratitis, red eyes, itching and burning. Systemic effects on haemodynamic parameters were small and of little clinical significance. However, subjects with cardiovascular or bronchospastic disease were excluded from most studies and thus it cannot be assumed that ocular levobunolol will not cause systemic effects in such patients. The recommended dose of levobunolol is 1 drop of the 0.5% solution instilled into the affected eye once or twice daily. Since the extent of absorption of ocular levobunolol in patients is unclear, as a matter of caution the same contraindications apply as with orally administered β-blockers.