P 326 Intraocular concentrations of mitomycin C: Are new devices for application beneficial?

&&v,w To assess the penetration of Iossrtan and L-158,338 into the rabbit eye after topical application and their effects on the IOP of ocular hypertensive cynomolgus monkeys. M&Q& Penetration was indirectly assessed in albino rabbits using an & assay. Aliquots of aqueous humor were sampled one hour after the bilateral topical instillation of one drop (50 uL) of 2% solutions of losartsn or L-158,338 (3Himid~o[4,5-B]pyridine,7-methyl-2-proI~yl-3~[[~-(IH-tetrazol-5-yl)[l,I’-biphenyl]4-yl]methyl]) and their ability to block 1251-[ser,1ie]-~11 (s.4tuLE) binding tc binding sites in a membrane fracticn of rabbit iris+ciliary body (ICB) was determined. IOP was measured out to six hours using a pneumatic tonometer in lightly sedated cynomolgus monkeys in which IOP had previously been experimentally elevated by photocoagulating the trabecular meshwork with an argon laser. &t&x Inhibition constants (Ki) for SARILE binding sites in ICB membranes were 80 nM and 2 nM for losartan and L-158.338, respectively. These results were in good agreement with values found at the ATI receptor subtype. In contrast a value of 72,000 nM was found for the AT2 selective compound WL-19. Concentrations in the aqueous humor were 50 nM and 120 nM for losertan and L-158,338, respectively. These values were 0.6and 60-fold their respective Ki values. The instiilation of 1% solutions of losattan .md L-158,338 did not elicit meaningful and consistent reductions in the IOP of ocuhu hypertensive monkeys. Increasing the dose of L-158,338 to 2% also failed to lower IOP. Conc[usions: AI1 receptors in the rabbit ICB are of the ATI subtype. Both topically applied losartan and L-158,338 penetrate into the rabbit eye hut neither agent displayed meaningful IOP lowering activity in ocular hypertensive monkeys.