A BIOAVAILABILITY COMPARISON IN RABBITS AFTER A SINGLE TOPICAL OCULARAPPLICATION OF PREDNISOLONE ACETATE FORMULATED AS A HIGH-VISCOSITY GEL AND AS AN AQUEOUS SUSPENSION .1.

To increase contact time between drug and ocular surface and thus impr ove the bioavailability, we used the high-viscous, water-soluble polym er carbomer Leogel (carbomer 0.5%). The drugs were applied to Copenhag en white rabbits as a single application. We compared the bioavailabil ity of prednisolone acetate 0.5% in Leogel with fusidic acid 1% after 1, 4, 7 and 10 h (n = 3 at each time points) with that obtained when d oubling the prednisolone acetate concentration in unchanged Leogel and fusidic acid 1% in 12 rabbits. In addition we compared the bioavailab ility of prednisolone acetate 0.5% given in 1) Leogel using fusidic ac id 1% with that obtained using 2) aqueous sulfacetamide sodium 10% as vehicle after 0.5, 1, 1.5, 2, 3, 6, 8 and 12 h (n = 6 at each time poi nts) in 54 rabbits. When doubling the prednisolone acetate dose an inc rease in bioavailability was achieved in conjunctiva, cornea and aqueo us humour with 1.57, 3.86 and 2.18 times, respectively. Prednisolone c oncentrations in cornea, conjunctiva and aqueous humour were higher us ing the Leogel vehicle than using the aqueous suspension. The bioavail ability in 0-12 h for prednisolone acetate in Leogel and fusidic acid 1% to conjunctiva was significantly higher (p = 0.003) than for predni solone acetate in aqueous and sulfacetamide sodium 10%. The bioavailab ility (0-6 h) for conjunctiva was significantly higher for the Leogel preparation than for the aqueous suspension (p<0.001). For cornea and aqueous humour, the bioavailability values for the total period (0-12 h) do not differ significantly. However, for the first 6 h the differe nce is significant (p<0.001 for cornea and p = 0.003 for aqueous humou r).