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Shellise Glogowski, Joel W. Proksch; Ocular and Systemic Pharmacokinetics of Loteprednol Etabonate Gel (0.5%) following Topical Ocular Administration to Rabbits. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6278.
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Loteprednol etabonate (LE) is a potent corticosteroid currently used to treat ocular inflammation in a variety of suspension formulations and in an ointment formulation. An ophthalmic LE gel formulation has been developed which is non-settling, and contains a lower concentration of BAK at a more physiological pH. This study investigated the ocular and systemic pharmacokinetics of LE following a single topical ocular dose of LE gel to rabbits.
Male Dutch Belted rabbits (n=40) received a single 35-μL topical ocular instillation of the test formulation into each eye, corresponding to an LE dose of 175 μg/eye. Over a 24-h period after dosing, animals were euthanized at pre-determined time intervals and selected ocular tissues were collected from each animal. Additionally, serial blood samples were also collected from one cohort of animals for plasma analysis. Concentrations of LE in ocular tissues and plasma were determined by mass spectrometry.
LE was rapidly absorbed and distributed within the eye, with measurable concentrations observed in ocular tissues within 5 min after dosing. Maximal concentrations of LE were achieved within 0.5 h in ocular tissues and 1.5 h in plasma following a single, topical ocular dose. Maximum concentrations of LE were highest in tear fluid (1560 μg/g), followed by bulbar conjunctiva (4.03 μg/g), cornea, (2.18 μg/g), iris/ciliary body (0.162 μg/g), and aqueous humor (0.0138 μg/mL). Concentrations of LE remained measurable in all ocular tissues through at least 12 h after dosing. In plasma, low but variable levels of LE were measurable through 4 h following dosing.
Topical ocular administration of an LE gel formulation provided rapid and sustained exposure to LE in ocular tissues with low systemic exposure in rabbits. These data are consistent with the efficacy results from Phase 3 studies of LE gel in postoperative inflammation and pain.
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