Distribution of a steroid antagonist in the eye following topical administration

The distribution of a steroid antagonist, RU486, that is known to reduce rabbit intraocular pressure has been examined in the eye. On an equal tissue weight basis, the corneal epithelium is the site of maximal absorption followed by conjunctival tissues (bulbar and palpebral) and the rest of the cornea. Aqueous humor concentrations of drug vary between 5 X 10(-6) and 5 X 10(-8) at 1 and 24 hours, respectively: these concentrations have been shown by others to inhibit dexamethasone binding to rat thymocytes, and are sufficient to act as an antagonist at steroid receptors in the eye. Multiple drop administration for 10 days (3 drops per day) revealed no accumulation in the treated eye, but did show the presence of drug in the untreated contralateral eye that could explain the contralateral pharmacological effect seen on intraocular pressure after several days of treatment.