0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A Highly Effective and Ultra-Long-Acting Anti-Glaucoma Drug, with a Novel Periorbital Delivery Method.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose: Two features define the future of glaucoma therapeutics: (1) greatly improved ocular hypotensive efficacy and (2) a delivery method that improves patient convenience and compliance. A highly efficacious and extraordinarily long-acting ocular hypotensive agent PGN 9856-isopropyl ester represents a potential next-generation anti-glaucoma drug. A new periorbital drug delivery route was also investigated. Methods: PGN 9856-isopropyl ester pharmacology was determined by employing human cells, including prostanoid receptor transfectants, and FLIPr or cellular dielectric spectroscopy technology. Intraocular pressure (IOP) was measured in conscious cynomolgus monkeys trained to accept pneumatonometry when under gentle restraint. For periorbital application, the compound was applied radially using a roller-ball device connected to a cylindrical reservoir. Pharmacokinetic data were obtained using LC/MS/MS instrumentation. Results: Single doses of PGN 9856-isopropyl ester, administered over a 0.001%-0.01% dose range, produced profound decreases in monkey IOP that persisted for at least 5 days, which was long after the drug was detectable in ocular tissues. It was not uncommon for a single eye drop to reduce IOP to the level of 4-7 mm Hg. Drug application to the periorbital dermis of ocular normotensive monkeys produced a similarly profound reduction in IOP, which was well maintained. Conclusions: PGN 9856-isopropyl ester appears to possess efficacy and duration of action properties unmatched by currently prescribed anti-glaucoma agents and by those currently undergoing clinical evaluation. In addition, application to the periorbital skin using a roller-ball device offers a more convenient method of ophthalmic drug delivery than eye drops and is noninvasive, unlike other "dropless" technologies.

          Related collections

          Author and article information

          Journal
          J Ocul Pharmacol Ther
          Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
          Mary Ann Liebert Inc
          1557-7732
          1080-7683
          Jun 2019
          : 35
          : 5
          Affiliations
          [1 ] 1 Department of Bioengineering, Imperial College London, South Kensington, London, England.
          [2 ] 2 JeniVision, Inc., Irvine, California.
          [3 ] 3 Asterand Ltd., Royston, England.
          [4 ] 4 Department of Ophthalmology and Biomedical Engineering, Duke University, Durham, North Carolina.
          [5 ] 5 Wincon Theracells Biotechnologies Co. Ltd., Nanning, China.
          [6 ] 6 Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska.
          [7 ] 7 Department of Ophthalmology and Visual Science, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
          Article
          10.1089/jop.2018.0126
          31025909
          3910b8be-45c6-4c3f-8cff-fb8ea9774e8f
          History

          EP receptor agonist,pharmacology,glaucoma animal model

          Comments

          Comment on this article