The anti-inflammatory efficacy and ocular hypertensive effect of
AL-2512 were characterized in rodent and feline models of ocular
inflammation. Neutrophil influx into ocular tissue following topical
ocular administration of test drugs was evaluated in models of
endotoxin-induced
uveitis. In rats, the anti-inflammatory efficacy of
AL-2512 was compared with that of 0.1%
dexamethasone. Test
drug or vehicle was administered topically before subplantar injection of
endotoxin. Neutrophil influx was assessed at 24 hours. Feline eyes, injected intravitreally with
endotoxin, were treated topically with 0.1%
AL-2512, 1.0%
prednisolone acetate or vehicle at various timepoints before and after
endotoxin injection. At 12 hours,
protein concentration and leukocyte count in aqueous humor were determined. In the feline intraocular pressure (IOP) model, after baseline IOP values were established,
AL-2512,
dexamethasone, or vehicle was administered topically to both eyes of cats. IOP was measured daily before and during treatment. Topical
ocular administration of
AL-2512 inhibited
endotoxin-induced leukocyte influx in rodent and feline models of
uveitis. In rats,
AL-2512 significantly inhibited neutrophil influx by 89%, compared with 93% by
dexamethasone. In feline eyes,
AL-2512 significantly (p < 0.05) inhibited leukocyte infiltration of aqueous humor by 59%, compared to 37% inhibition by
prednisolone acetate. Intraocular pressure in cats treated for 32 days with
AL-2512 or
dexamethasone increased 6% and 18%, respectively. The ocular anti-inflammatory effect of
AL-2512 was equivalent to
dexamethasone and superior to
prednisolone acetate in rat and feline models of ocular
inflammation, respectively. This
steroid provides anti-inflammatory efficacy equivalent to
dexamethasone with a reduced risk of inducing
ocular hypertension.