title: Comparison of concentration-time profiles of levobunolol and timolol in anterior and posterior ocular tissues of albino rabbits.
abstract: The potential effects of anti-glaucoma drugs, such as levobunolol and timolol, on blood flow in the posterior segment of the eye are of great interest in terms of changes in optic nerve head perfusion and prevention of visual field loss. These effects are related to the rate and extent of their absorption into the site of action. In this study, the concentrations of timolol and levobunolol in the aqueous humor, iris-ciliary body, vitreous humor, choroid-retina, and optic nerve were compared following instillation of a single drop of 0.5% ophthalmic solutions into albino rabbit eyes. Tissue drug and metabolite concentrations were measured by liquid chromatography-mass spectrometry. Dihydrobunolol (DHB) is an equipotent metabolite of levobunolol. In the anterior segment of the eye, levobunolol plus DHB concentrations were higher than timolol concentrations in aqueous humor and were comparable to those of timolol in iris-ciliary body. However, in the choroid-retina and optic nerve, timolol concentrations were greater than those of levobunolol plus DHB. Overall, the study demonstrates comparable concentrations of levobunolol and timolol in the anterior section of the eye. The low availability of levobunolol in the posterior segment as compared to timolol may be a key advantage for levobunolol in producing less adverse effect on blood flow in the choroid-retina and optic nerve.
authors.affiliation: Department of Pharmacokinetics, Allergan, Inc., Irvine, California, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Acheampong
authors.forename: A
authors.initials: A
authors.lastname: Breau
authors.forename: M
authors.initials: M
authors.lastname: Shackleton
authors.forename: W
authors.initials: W
authors.lastname: Luo
authors.forename: S
authors.initials: S
authors.lastname: Lam
authors.forename: D D
authors.initials: DD
authors.lastname: Tang-Liu
mesh_terms: D000042:Absorption; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002829:Choroid / Q000378:metabolism; D002924:Ciliary Body / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D007498:Iris / Q000378:metabolism; D002040:Levobunolol / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions; D009900:Optic Nerve / Q000378:metabolism*; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D013999:Timolol / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; C015810:dihydrobunolol; D013999:Timolol; D002040:Levobunolol