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L David Waterbury, Vince Florio; Estimating Total Dose Received by an Ophthalmic Irrigation Solution Used during Cataract Surgery. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1093.
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© ARVO (1962-2015); The Authors (2016-present)
Published methods for determining the total dose received with an ophthalmic irrigation solution are not available. We report a method for estimating the total dose received by canines in a pharmacokinetic study. The total dose received is important to compare accurately with topical dosing and with systemic exposure.
A formulation of ketorolac (0.3%) and phenylephrine (1%) was administered in irrigation solution in 20 canines during lens replacement surgery. Ketorolac concentrations were determined by LC/MS in aqueous, cornea, conjunctiva, iris-ciliary body, vitreous, retina, choroid, retinal pigment epithelium, sclera, lens capsule and plasma from 4 dogs per time point (0, 2, 6, 8 and 10 hours post-surgery). The tissue weights were obtained upon careful dissection of the tissues, except for aqueous and vitreous samples which were obtained prior to freezing of tissues. The concentrations determined were multiplied by the tissue weights and, for plasma concentrations, by the calculated plasma volume based on the age and weight of the dogs. These calculated values for each animal were summed to determine the estimated total dose of ketorolac received.
The total dose received via intracameral administration in canines was determined to be 12.8 µg, which is less than 10% of the amount received by a 50-µL dose of topical ketorolac. Thus, the amount of systemic exposure of ketorolac is less by the intracameral irrigation route than by topical administration as reflected by 2- to 5-fold lower plasma concentrations. Nonetheless, compared to topical dosing, intracameral delivery provided 2- to 10-fold higher levels of ketorolac in ocular tissues, which is sufficient to inhibit both COX-1 and COX-2 in aqueous and vitreous ten hours after dosing. Also unlike topical dosing, administration via ophthalmic irrigation provides therapeutic concentrations in the vitreous.
A method for estimating the total dose of an ophthalmic drug in an irrigation solution is relevant for determining total systemic exposure to ketorolac. This method is useful as it allows the comparison with topical dosing. Dosing by intracameral irrigation during the surgical procedure provides superior therapeutic concentrations in target ocular tissues at a 90% lower rate of systemic exposure compared to topical dosing.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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