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Abstract #46356 Published in IGR 13-3
Trabecular meshwork and lens partitioning of corticosteroids: implications for elevated intraocular pressure and cataracts
Thakur A; Kadam R; Kompella UBArchives of Ophthalmology 2011;
OBJECTIVE: To determine whether adverse effects such as elevated intraocular pressure and cataracts, which are lower with dexamethasone when compared with fluocinolone acetonide or triamcinolone acetonide, may be explained in part by the differences in drug lipophilicity and partitioning of these drugs into the trabecular meshwork and lens. METHODS: The n-octanol/phosphate-buffered saline (pH 7.4) partition coefficient (log distribution coefficient [D]) and bovine/human ocular tissue partition coefficients were determined for triamcinolone, prednisolone, dexamethasone, fluocinolone acetonide, triamcinolone acetonide, and budesonide at 37°C. RESULTS: The log D of the corticosteroids ranged from 0.712 to 2.970. The ranges of tissue:PBS partition coefficients following drug incubation at 0.4, 2.0, and 10.0 μg/mL were 0.35 to 1.56, 0.30 to 2.12, and 0.30 to 1.95, respectively, for the bovine lens, 0.87 to 4.18, 0.71 to 4.40, and 0.69 to 5.86, respectively, for the human lens, and 2.98 to 9.48, 2.41 to 9.16, and 1.71 to 9.96, respectively, for the bovine trabecular meshwork. In general, tissue partitioning showed a positive correlation with log D. Dexamethasone, with lipophilicity less than triamcinolone acetonide and fluocinolone acetonide, exhibited the least amount of partitioning in the trabecular meshwork and lens among these 3 corticosteroids commonly used for treating diseases at the back of the eye. CONCLUSION: Binding of corticosteroids to the trabecular meshwork and lens increases as drug lipophilicity increases. CLINICAL RELEVANCE: Less lipophilic corticosteroids with limited partitioning to the trabecular meshwork and lens may result in reduced incidence of elevated intraocular pressure and cataracts.
Nanomedicine and Drug Delivery Laboratory, Department of Pharmaceutical Sciences, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
9.4.1 Steroid-induced glaucoma (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)
9.4.4.5 Other (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders > 9.4.4 Glaucomas associated with disorders of the lens)
