Intraocular penetration of topically applied [14C]fosfonet sodium in rabbits

The intraocular penetration of [14C]fosfonet was studied following topical application of 25 mg of an ointment containing 5% [14C]fosfonet sodium onto the intact and abraded eyes of New Zealand white rabbits. Radioactivity penetrated rapidly through the abraded cornea and entered the anterior chamber. The concentration of fosfonet in the aqueous humor peaked at 7.2 microgram/ml by 90 min. Assuming an aqueous humor volume of 300 microliter, this level would correspond to approximately 0.2% of the applied dose. The highest concentration of fosfonet found in the abraded cornea was 0.3 microgram/mg, or 0.4% of the applied dose. The half-lives for the elimination of fosfonet from the aqueous humor and cornea were about 2.5 and 2.7 hr, respectively. The fosfonet levels in the iris were extremely low throughout the 6-hr period. The penetration of [14C]fosfonet through the intact cornea was considerably less than that found in the abraded eye. The peak concentrations of fosfonet in the aqueous humor and cornea of the intact eye were 0.26 microgram/ml and 0.02 microgram/mg, respectively, and occurred within 10 min of application of ointment.