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S. Glogowski, J. W. Proksch; Ocular Pharmacokinetics of Loteprednol Etabonate Following Ocular Administration of a Novel Ointment Formulation or a Suspension (Lotemax®) in Rabbits With Corneal Inflammation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1980.
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© ARVO (1962-2015); The Authors (2016-present)
Loteprednol etabonate (LE) is a potent corticosteroid currently marketed as a suspension formulation (Lotemax®) for the treatment of ocular inflammation. The ocular and systemic pharmacokinetics of LE and two metabolites were investigated following topical administration of a novel LE ointment formulation and compared with the marketed Lotemax suspension formulation in pigmented rabbits with corneal inflammation.
Ocular inflammation was induced in Fauve de Bourgogne rabbits with a single 30-µL intrastromal injection of clove oil. The following day, rabbits received a single topical ocular dose of 50 µL of either the 0.5% LE ointment formulation or the marketed 0.5% suspension formulation (Lotemax, Bausch & Lomb, Inc.). At various time intervals after dosing, rabbits were euthanized, and ocular tissues and plasma were collected. Concentrations of LE and two metabolites (PJ-91 and PJ-90) were determined by LC/MS/MS.
LE was rapidly absorbed and distributed to ocular tissues following topical ocular administration of the ointment formulation to pigmented rabbits. Administration of the ointment formulation afforded similar ocular and systemic exposure to LE and its metabolites compared with the currently marketed Lotemax suspension formulation. In the marketed suspension formulation, maximal LE concentrations in conjunctiva, cornea, and aqueous humor were 2.06 µg/g, 1.16 µg/g, and 0.0724 µg/mL, respectively. In the ointment formulation, maximal concentrations in conjunctiva, cornea, and aqueous humor were 3.62 µg/g, 1.40 µg/g, and 0.0293 µg/mL, respectively. Concentrations of LE in plasma were equivalent for both formulations, with maximal LE concentrations ≤ 0.354 ng/mL. Ocular exposure to two metabolites, PJ-91 and PJ-90, was somewhat greater with the suspension formulation compared with the ointment formulation.
Topical administration of LE in a novel ointment formulation provided LE exposure in ocular tissues and plasma that was similar to that afforded by Lotemax (LE ophthalmic suspension, 0.5%) in rabbits with ocular inflammation.
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