| Autor: |
Woodward DF; Department of Bioengineering, Imperial College London, South Kensington, United Kingdom.; JeniVision, Inc., Irvine, California, USA., Coleman RA; Asterand Ltd. Royston, Herts, England., Woodrooffe AJ; Asterand Ltd. Royston, Herts, England., Spada CS; Clayton Spada Visual Communications, Beijing, China., Wang JW; JeniVision, Inc., Irvine, California, USA. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics [J Ocul Pharmacol Ther] 2020 Oct; Vol. 36 (8), pp. 636-648. Date of Electronic Publication: 2020 Jul 08. |
| DOI: |
10.1089/jop.2020.0033 |
| Abstrakt: |
Purpose: JV-GL1 is an efficacious, potent, and long-acting antiglaucoma agent, according to studies in ocular normotensive and hypertensive monkeys. As an obligatory step in the drug development process, studies with exaggerated doses and an accelerated dosing schedule for JV-GL1 were performed in a second species (dog). Methods: Intraocular pressure (IOP) was measured by pneumatonometry in conscious Beagle dogs, which remained conscious throughout the study and gently restrained by hand. Pupil diameter was measured with an Optistick. Ocular surface hyperemia was visually assessed and scored according to a 1-3 assessment scale. Results: JV-GL1, as a 0.01% eye drop, produced significantly greater reductions in IOP than the original clinical dose of bimatoprost (0.03%). JV-GL1 and its free acid enzymatic hydrolysis product PGN 9856, over a 0.01%-0.1% dose range, reduced IOP to ≤10 mm Hg. JV-GL1 and PGN 9856 produced no miosis but a similar degree of ocular surface hyperemia to bimatoprost. Although PGN 9862, a close congener of PGN 9856, was very active as the free acid, esterification essentially abolished its ocular hypotensive activity and ocular surface redness. Conclusion: JV-GL1 was confirmed as a highly effective and potent ocular hypotensive, exceeding the activity of bimatoprost. A similar degree of ocular surface redness was apparent for both compounds, given as eye drops, but no other effects occurred. Results with PGN 9862 and its isopropyl ester confirmed that PGN 9862-isopropyl ester is not bioavailable in the eye and not susceptible to enzymatic hydrolysis in ocular tissues, a first for C1 ester prodrugs in the eye. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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