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Kathryn Crawford, Jeanne Ellis, Jack Rulander, Stephen Johnston, Francis Lai, Edward Ellis, Charles Leahy; Sustained Delivery of Prostaglandin from Drug-Containing Depots Using Ocular Rings in Beagles. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5073.
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To evaluate the efficacy of sustained-release latanoprost from depots in a topical ophthalmic drug delivery device (TODDD™).
The right eyes of 8 ocular normotensive adult beagle dogs were fitted with ocular ring devices, each containing 2 latanoprost-drug depots (cylindrical cores, 600 μg latanoprost). The depots were matched in volume and surface release area to those of a human-configured device. A device with blank depots containing no latanoprost was placed on the right eye of 1 additional animal. All left eyes remained untreated. Clinical slit-lamp exams were performed pre-placement on Day 1 and post-placement on Days 1, 8 and 17. Daily observations were performed to assess the presence of the device (retention) and any ocular abnormalities. Intraocular pressure (IOP) and pupil diameter were measured pre- and post- placement on Day 1, and on Days 4, 8, and 16. Plasma samples were collected on Day 1 prior to, and approximately 4 hours after device insertion, and on Day 8. Tear samples were collected on Day 16 by Schirmer strip in the lower cul-de-sac. Tear and plasma samples were analyzed by LC/MS/MS for latanoprost and latanoprost acid. The lower limit of quantitation was 0.5 ng/mL.
IOP reduction in the treated eye compared to the control eye was approximately 3 mmHg on Day 4 (n=6) and Day 8 (n=4), and 7 mmHg on Day 16 (n=3) in the dogs that had retained the latanoprost-loaded devices, representing a 37% reduction in normotensive IOP from baseline. There was no effect on IOP in the animal wearing the placebo device. The IOP returned to baseline levels in all eyes after removal of the devices. A range of 25 - 215 ng/mL latanoprost was recovered from the tears of animals wearing the drug devices. No latanoprost was detected in plasma or in the tear samples from untreated eyes.
Long-term retention of this ring device configuration and dimensions in this species was not achieved, but this study demonstrates the therapeutic feasibility of the sustained-release (non-ring) TODDD™ configured for human ocular dimensions. In vitro analysis of the worn devices and of the extended latanoprost release profile from new devices relative to tear levels measured at Day 16 indicates that sustained IOP-lowering could be achieved over a 2-3 month time period.
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