The ocular hypotensive effects of demeclocycline, tetracycline and other tetracycline derivatives

Demeclocycline, tetracycline and other tetracycline derivatives lowered intraocular pressure (IOP) in rabbits following intravitreal injection, but the onset of this effect was not evident until 1 or more days after drug administration. Of the drugs tested, demeclocycline was the most active ocular hypotensive agent. Demeclocycline caused a dose-dependent decrease in IOP. The maximum IOP decrease of approximately 12 mm Hg occurred 5 days after intravitreal administration of 0.5 mg, with the effect persisting for over a week. Demeclocycline did not alter tonographically measured aqueous humor outflow facility or episcleral venous pressure. Based on calculated aqueous humor flow rates following 0.2 mg demeclocycline, a 62% decrease in aqueous humor formation occurred 7 days after intravitreal injection. The flow-to-diffusion ratio for ascorbate was reduced 54% 6 days after the intravitreal administration of demeclocycline, a change also consistent with suppression of aqueous humor formation. Anterior chamber aqueous humor protein concentration was increased 6 days after demeclocycline administration. No histologic changes were present in the treated eyes by light microscopy. Intravitreal demeclocycline similarly lowered IOP in cats, with the duration of effect lasting up to 20 days.