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M. Attar, R. M. Schiffman, L. Borbridge, Q. Farnes, D. Welty; Evaluation of the Pharmacokinetics of Ketorolac Ophthalmic Solutions in Rabbit. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1989.
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Ketorolac ophthalmic solutions containing the preservative benzalkonium chloride are available for 4-times-daily administration (QID) as 0.4% and 0.5% aqueous solutions, pH = 7.4. This study evaluated the pharmacokinetics of a newly formulated, preservative-free 0.45% ketorolac solution, pH = 6.8, containing carboxymethylcellulose (CMC), developed to treat pain and inflammation following cataract surgery.
Bilateral ocular instillations of ketorolac ophthalmic solutions were administered to rabbits. Aqueous humor and iris ciliary body tissues were extracted, and concentrations of ketorolac were determined using liquid chromatography-tandem mass spectrometry.
A novel CMC-based 0.45% ketorolac formulation increased ocular bioavailability by approximately 200% in aqueous humor and 300% in the iris-ciliary body relative to the 0.4% ketorolac formulation. In aqueous humor, the CMC-based 0.45% ketorolac formulation increased the maximum concentration (Cmax) from 211 to 389 ng/mL and area under the concentration time curve (AUC0-t) from 465 to 939 ng•hr/mL compared to the 0.4% ketorolac formulation. In iris-ciliary body, the CMC-containing 0.45% ketorolac solution increased Cmax from 216 to 450 ng/g and AUC0-t from 699 to 2040 ng•hr/g compared to the 0.4% ketorolac formulation. In pharmacokinetic simulations, twice daily (BID) administration of the CMC-based 0.45% ketorolac solution demonstrated higher ketorolac concentrations compared to QID administration with 0.4% ketorolac solution.
A novel CMC-containing formulation of 0.45% ketorolac improved ocular delivery of active drug. This ketorolac formulation permits dosing of BID vs QID.
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