Distribution of 14C-Latanoprost Following a Single Intracameral Administration Versus Repeated Topical Administration.

Abstract

PurposeTo qualitatively evaluate the ocular and periocular distribution of 14C-latanoprost following a single intracameral administration or repeated topical ocular administration in beagle dogs and cynomolgus monkeys.MethodsIn the dog study, three animals received an intracameral dose of 14C-latanoprost bilaterally and were euthanized at 1, 2, and 4 h post dose; three control animals received topical 14C-latanoprost bilaterally once daily for 5 days and were euthanized at 1, 4, and 24 h post final dose. Sagittal 40-µm sections of eyes with surrounding tissues were collected and processed for autoradiography. Methods in the monkey study were similar; two animals received a unilateral intracameral dose of 14C-latanoprost.ResultsAfter intracameral dosing in dogs, radioactivity was concentrated in the cornea, iris, ciliary body, and anterior chamber with no radioactivity detected in the eyelids or other periorbital tissues. After topical dosing, radioactivity was distributed in the bulbar conjunctiva, cornea, anterior chamber, iris, ciliary body, upper and lower eyelids, and periorbital tissues (fat/muscle). After intracameral dosing in monkeys, radioactivity was concentrated in the anterior chamber, cornea, iris, ciliary body, and posteriorly along the uveoscleral outflow pathway; there was no radioactivity in the eyelids or periorbital tissues aside from signal in the nasolacrimal duct, likely from reflux of 14C-latanoprost into the tear film.ConclusionsIntracameral delivery resulted in more selective target tissue drug exposure. Intracameral drug delivery has potential to reduce ocular surface and periocular adverse effects associated with topical administration of prostaglandin analogues, such as eyelash growth and periorbital fat atrophy.Electronic supplementary materialThe online version of this article (10.1007/s40123-020-00285-3) contains supplementary material, which is available to authorized users.