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Miltiadis K Tsilimbaris, Stella Blazaki, Antonios Stratidakis, Irini Naoumidi, Christos Tsatsanis, Manolis Tzatzarakis, Aristidis Tsatsakis; Pharmacokinetics of intravitreal indomethacin. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2032.
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Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat posterior segment inflammation. In this study we evaluated the intravitreal bioavailability of indomethacin in rabbit eyes.
Pigmented animals were used to analyze the pharmacokinetics of intravitreal indomethacin. All eyes were injected with 250μg/ml (0,1ml per injection) of indomethacin. Vitreous, aqueous humor and retina/choroid drug levels were analyzed at specific time points (0h, 0.5h, 1h, 3h, 12h, 24h). After euthanasia of the animals, samples were prepared and analyzed by means of HLPC/MS method. Slit lamp examination, intraocular pressure (IOP) measurements and indirect fundoscopy were performed prior to any injection and at each time point.
No adverse events were observed during pharmacokinetics assessment. No signs of inflammation, hemorrhage or detachment were detected. The levels of IOP were within normal limits and no cataract formation was observed. The clearance of indomethacin follows first order kinetics in aqueous, vitreous and retina/choroid samples. The half-life of indomethacin solution estimated in vitreous1,36 hours with an elimination constant rate (K) of 0,511, in aqueous humor 1,44 hours with K of 0,482 and in retina/choroid 1,41 hours with an el K of 0,491. The maximum concentration (Cmax) was estimated in vitreous 6,13μg/ml, in aqueous 0,40μg/ml and in retina/choroid 136,69μg/ml.
Indomethacin demonstrated excellent penetration into the retina/choroid. However, the half-life of indomethacin remains short and so there is a need for greater prolongation of its presence in the vitreous cavity by means of sustained delivery systems.
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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