A bioavailability comparison in rabbits after a single topical ocular application of prednisolone acetate formulated as a high-viscosity gel and as an aqueous suspension.
To increase contact time between drug and ocular surface and thus improve the bioavailability, we used the high-viscous, water-soluble polymer carbomer Leogel (carbomer 0.5%). The drugs were applied to Copenhagen white rabbits as a single application. We compared the bioavailability 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 doubling the prednisolone acetate concentration in unchanged Leogel and fusidic acid 1% in 12 rabbits. In addition we compared the bioavailability of prednisolone acetate 0.5% given in 1) Leogel using fusidic acid 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 points) in 54 rabbits. When doubling the prednisolone acetate dose an increase in bioavailability was achieved in conjunctiva, cornea and aqueous humour with 1.57, 3.86 and 2.18 times, respectively. Prednisolone concentrations in cornea, conjunctiva and aqueous humour were higher using the Leogel vehicle than using the aqueous suspension. The bioavailability in 0-12 h for prednisolone acetate in Leogel and fusidic acid 1% to conjunctiva was significantly higher (p = 0.003) than for prednisolone acetate in aqueous and sulfacetamide sodium 10%. The bioavailability (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 difference is significant (p < 0.001 for cornea and p = 0.003 for aqueous humour).
Johansen
S
S
Eye Pathology Institute, University of Copenhagen, Denmark.
Rask-Pedersen
E
E
Prause
J U
JU
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D003228:Conjunctiva / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D005260:Female; D005672:Fusidic Acid / Q000493:pharmacokinetics; D005782:Gels; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011817:Rabbits; D013409:Sulfacetamide / Q000493:pharmacokinetics; D013535:Suspensions
D000900:Anti-Bacterial Agents; D005782:Gels; D005938:Glucocorticoids; D009883:Ophthalmic Solutions; D013535:Suspensions; D013409:Sulfacetamide; D005672:Fusidic Acid; C009935:prednisolone acetate; D011239:Prednisolone