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

Abstract

Purpose: To qualitatively evaluate the ocular and periocular distribution of 14 C-latanoprost following a single intracameral administration or repeated topical ocular administration in beagle dogs and cynomolgus monkeys. Methods: In the dog study, three animals received an intracameral dose of 14 C-latanoprost bilaterally and were euthanized at 1, 2, and 4 h post dose; three control animals received topical 14 C-latanoprost bilaterally once daily for 5 days and were euthanized at 1, 4, and 24 h post final dose. Sagittal 40-lm 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 14 Clatanoprost. Results: After 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 14 C-latanoprost into the tear film. Conclusions: Intracameral 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. Digital Features This article is published with digital features to facilitate understanding of the article. You can access the digital features on the article's associated Figshare page. To view digital features for this article go to

Development of an in vitro model to estimate mass transfer from the anterior cavity

“…Topical administration often displays limited bioavailability (<5%) (Schopf et al, 2015) due to physical and biochemical barriers (Awwad et al, 2017a) including the pre-corneal tear film, the structure and biophysiological properties of the cornea, the limited volume that can be accommodated by the cul-de-sac, the lacrimal drainage system and reflex tearing. Patient nonadherence to eyedrops includes difficulty and forgetfulness in instilling eyedrops (Shen et al, 2020). Other routes of administration, such as intracameral delivery directly into the anterior chamber, have been reported to reduce systemic and corneal side effects that commonly arise with topical eyedrop steroid therapy (Shah et al, 2018).…”