Ocular Tissue Distribution of Ketorolac After Administration of OMS302 to Dogs During IOL Replacement
Purpose
To determine concentrations of KE in retina and other ocular tissues following intracameral administration of OMS302 during ILR in dogs. Using published IC50 values for cyclooxygenase (COX) inhibition by KE (Waterbury et al. Curr Med Res Opin. 2006 Jun;22(6):1133-40), estimates of percent inhibition were derived for each time point.
Methods
ILR by phacoemulsification was performed on 20 female beagles. During the procedure, OMS302, a drug recently FDA approved for use during ILR and containing 480 µM phenylephrine/89 µM ketorolac, was administered in BSS solution via irrigation and intracameral injection immediately post-procedure. Four animals per time point were sacrificed at 0, 2, 6, 8, and 10 hours post-procedure. Samples of blood and aqueous humor were collected. Enucleated eyes were frozen and dissected for collection of retina, RPE-choroid, cornea, iris-ciliary body, vitreous humor, sclera, and lens capsule. Tissue concentrations of KE were quantitated using a liquid chromatography/mass spectrometry method.
Results
KE concentrations in the retina were 1400 ± 1004 ng/g immediately following the end of ILR/ intracameral injection and 164 ± 39 ng/g at eight hours post-procedure, corresponding to estimated COX-1/COX-2 inhibition of 99.3%/96.0% at t = 0, and 98.4%/91.1% at t= 8 hours. The retinal half-life was ~ 3.8 hr. Tissue concentrations in aqueous humor, vitreous humor, and RPE-choroid at t = 8 hours were consistent with > 90% inhibition of COX-1 and COX-2. The mean plasma level of KE was 4.73 ± 1.46 ng/mL at t = 0, declining to undetectable levels at t ≥ 2 hours.
Conclusion
In this study, the use of OMS302 during ILR surgery resulted in the uptake of KE by retina and other ocular tissues at levels sufficient to inhibit COX-1 and COX-2 by 90% for at least 8 hours. Systemic exposure was low and transient.