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The effect of alginic acid addition to 1% or 2% carteolol solutions on the ocular penetration of the drug has been evaluated in the pigmented rabbit. During single dose studies, an increase in bioavailability ranging from 40% to 60% was observed in the aqueous humor and in the iris-ciliary body. During repeated dose studies, this increased ocular bioavailability of carteolol in the presence of alginic acid led to an equivalent concentration in the target tissue, although the dosage was only once a day compared with twice a day for the usual carteolol eyedrops. [sup 14]C-carteolol distribution studies demonstrated the binding of carteolol in pigmented ocular tissues. Thus, the presence of alginic acid as a new excipient supports a possible decrease in dosage regimen, while retaining sufficient ocular bioavailability to lower intraocular pressure. [ABSTRACT FROM AUTHOR]

Alginic acid was evaluated as a potential vehicle in ophthalmic solutions for prolonging the therapeutic effect of carteolol. This anionic vehicle was expected to slow down drug elimination by the lacrimal flow, both by undergoing in-situ gel formation and by interacting with the mucus. In vitro studies indicated that carteolol is released slowly from alginic acid formulations, suggesting an ionic interaction. The adhesive behavior of alginic acid solution was better than that of another polymer, hydroxyethylcellulose (HEC). Intraocular pressure (IOP) measurements of rabbit eyes treated with a 1% carteolol formulation with or without alginic acid showed that this polymer significantly extended the duration of the pressure-reducing effect of carteolol to 8 h. The increased ocular bioavailability of 1% carteolol in the presence of alginic acid led to an equivalent concentration in the target tissue although administration was only once a day compared with twice a day for 1% carteolol alone. The overall results of this study indicate that the alginic-acid vehicle is an excellent drug carrier, well tolerated, and could be used for the development of a long-acting ophthalmic formulation of carteolol.

An experimental model of optic nerve ischemia was designed in the rabbit to determine early biochemical alterations, i.e.--changes of high energy phosphate metabolites (ATP and phosphocreatine)--in occlusive and peri-occlusive areas. Vascular occlusion provoked a rapid fall of ATP and phosphocreatine in the optic nerve. Free radicals scavengers, superoxide dismutase plus catalase or dimethylthiourea were able to counteract the drop of phosphate metabolites in the peri-occlusive area. These results show that hypoxia leads to oxygen-derived free radical generation which can be responsible for cell damage and emphasize the role of free radicals in the pathogenesis of ocular diseases related to vascular dysfunction.

Since oxidative stress is a well substantiated hypothesis of cataract pathogenesis, screening was performed in acellular systems in order to select scavengers of reactive oxygen species; the selected compounds are at present being tested in lens culture and in animal models.