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Charles D Blizzard, Ankita Desai, Shelby D'Abbraccio, Jessica Mangano, Jennifer Langh, Noah Buff, Jamie Lynne Metzinger, Michael H Goldstein, Ann Gelormini, Arthur Driscoll; Efficacy and Pharmacokinetics of a Sustained Release Travoprost Intracameral Hydrogel Implant in Beagle Dogs. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1245.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the efficacy and pharmacokinetic (PK) profile of travoprost release from an intracameral hydrogel implant, OTX-TIC, over 7 months.
OTX-TIC was injected into the anterior chamber (AC) of 6 beagle dogs (n=12 eyes) using a 27g needle and aqueous humor (AH) samples were collected pre-dose (Day 0) and post-dose (29, 59, 92, 120, 148, 183 and 211 days). Intraocular pressure (IOP) and pupil diameter were measured over the study duration to assess efficacy; visual monitoring and ultrasound conferred retention and implant location. Drug concentrations in the AH was measured by liquid chromatography coupled with a tandem mass spectrometry (LC/MS/MS).
OTX-TIC is formulated to release travoprost with zero-order kinetics for 4 months. As expected post-injection, travoprost ester was converted into the pharmacologically active travoprost free acid (TFA) form in vivo. The sustained TFA concentrations in beagle AH were an average of 1.1 ng/mL (+/-0.2 ng/mL) from Days 30 through 120 days, and then the values drop to 0.1 ng/mL by Day 148 and then below the LOQ (0.05 ng/mL). Mean IOP measured 19.5±1.6 mmHg at baseline and then demonstrated a mean >25% reduction post-administration to 14.3±0.6 mmHg through 120 days. Travoprost, a miotic agent in beagles, demonstrated strong pupil constriction post-administration, which was sustained for 120 days with a return to near baseline values by study completion. Visual monitoring of OTX-TIC in the AC demonstrated the implants resided between the 5:00 to 7:00 positions in the inferior angle for the duration of the study with no implant corneal contact noted in any animal. The median persistence of OTX-TIC in beagle eyes was between 120 and 134 days, and all implants were absent at 148 days.
OTX-TIC shows promise as a sustained release glaucoma treatment based on the residence in the inferior angle, consistent TFA concentrations in AH over 120 days, pupillary constriction in the beagle, and sustained IOP-lowering; it was resorbed shortly thereafter. The implant was well-tolerated.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Efficacy of OTX-TIC, demonstrated by sustained mean IOP decrease and mean pupil diameter measurement
Visual monitoring of OTX-TIC using fluorescein and ultrasound; implants reside in the iridocorneal angle
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