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Jennifer Seal, Shamira Perera, Michael Coote, Michael R Robinson, Patrick M Hughes, Alazar N Ghebremeskel, James A Burke, Mayssa Attar; Intracameral Administration of a Sustained Release Bimatoprost Implant Efficiently Delivers Bimatoprost to Target Tissue Reducing Risk of Topical Prostaglandin Analog- Associated Adverse Events. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3022.
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© ARVO (1962-2015); The Authors (2016-present)
To compare the ocular distribution of bimatoprost in dogs and safety in glaucoma patients after intracameral injection of a biodegradable sustained release bimatoprost implant (BimSR) vs repeated topical administration of bimatoprost 0.03% ophthalmic solution (generic formulation concentration).
Both eyes of 24 beagle dogs were administered bimatoprost 0.03% once daily for 7 days or an intracameral BimSR implant containing 15 μg bimatoprost. Ocular and periocular tissues were collected at relevant time points and bimatoprost concentrations were measured using liquid chromatography/tandem mass spectrometry and high-performance liquid chromatography. Prostaglandin analog (PGA) -associated ocular adverse events (AEs) or findings were evaluated from a 6 month interim analysis of a phase 1/2 clinical trial in 75 glaucoma patients receiving a BimSR injection in the study eye and daily topical bimatoprost in fellow eye.
After BimSR administration in dogs, bimatoprost distributed primarily to tissues adjacent to the implant (ie iris-ciliary body [ICB], cornea, and aqueous humor); after topical bimatoprost administration the highest bimatoprost concentrations were found in ocular surface tissues (ie eyelid margins, bulbar conjunctiva, periorbital fat, cornea). Maximal bimatoprost concentration in ICB (target tissue) was higher after BimSR than after topical dosing. In glaucoma patients, PGA use-related AEs were more common in eyes treated with topical bimatoprost than in eyes treated with BimSR. Conjunctival hyperemia (onset later than 2 days) after BimSR injection was reported in 6.7% of study eyes compared with 17.6% of fellow eyes; eyelash growth was reported in no study eyes and 2.7% of fellow eyes. Orbital fat atrophy was observed in 2 patients in the fellow eye only receiving topical bimatoprost.
BimSR targeted the bimatoprost delivery to the ICB efficiently and more selectively than topical administration. Bimatoprost levels in bulbar conjunctiva, eyelid margin, and periorbital fat (potential AE associated tissues) were remarkably reduced or undetectable with BimSR. Consistent with this, compared with topical bimatoprost, BimSR was associated with reduced incidence of PGA use-related AEs in glaucoma patients in a phase 1/2 clinical trial.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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