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

David F. Woodward, Jenny W. Wang, Robert A. Coleman, Amanda J. Woodrooffe, Kenneth L. Clark, W. Daniel Stamer, Guoxian Tao, Shan Fan, Carol B. Toris

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)265-277
Number of pages13
JournalJournal of Ocular Pharmacology and Therapeutics
Volume35
Issue number5
DOIs
StatePublished - Jun 2019

Fingerprint

Glaucoma
Intraocular Pressure
Esters
Pharmaceutical Preparations
Ophthalmic Solutions
Haplorhini
Technology
Dielectric Spectroscopy
Equipment and Supplies
Macaca fascicularis
Dermis
Patient Compliance
Prostaglandins
Pharmacokinetics
Pharmacology
Skin
Therapeutics

Keywords

  • EP receptor agonist
  • glaucoma animal model
  • pharmacology

ASJC Scopus subject areas

  • Ophthalmology
  • Pharmacology
  • Pharmacology (medical)

Cite this

A Highly Effective and Ultra-Long-Acting Anti-Glaucoma Drug, with a Novel Periorbital Delivery Method. / Woodward, David F.; Wang, Jenny W.; Coleman, Robert A.; Woodrooffe, Amanda J.; Clark, Kenneth L.; Stamer, W. Daniel; Tao, Guoxian; Fan, Shan; Toris, Carol B.

In: Journal of Ocular Pharmacology and Therapeutics, Vol. 35, No. 5, 06.2019, p. 265-277.

Research output: Contribution to journalArticle

Woodward, David F. ; Wang, Jenny W. ; Coleman, Robert A. ; Woodrooffe, Amanda J. ; Clark, Kenneth L. ; Stamer, W. Daniel ; Tao, Guoxian ; Fan, Shan ; Toris, Carol B. / A Highly Effective and Ultra-Long-Acting Anti-Glaucoma Drug, with a Novel Periorbital Delivery Method. In: Journal of Ocular Pharmacology and Therapeutics. 2019 ; Vol. 35, No. 5. pp. 265-277.
@article{b849c0ee9a524a899a6e8252f5867b87,
title = "A Highly Effective and Ultra-Long-Acting Anti-Glaucoma Drug, with a Novel Periorbital Delivery Method",
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.",
keywords = "EP receptor agonist, glaucoma animal model, pharmacology",
author = "Woodward, {David F.} and Wang, {Jenny W.} and Coleman, {Robert A.} and Woodrooffe, {Amanda J.} and Clark, {Kenneth L.} and Stamer, {W. Daniel} and Guoxian Tao and Shan Fan and Toris, {Carol B.}",
year = "2019",
month = "6",
doi = "10.1089/jop.2018.0126",
language = "English (US)",
volume = "35",
pages = "265--277",
journal = "Journal of Ocular Pharmacology and Therapeutics",
issn = "1080-7683",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - A Highly Effective and Ultra-Long-Acting Anti-Glaucoma Drug, with a Novel Periorbital Delivery Method

AU - Woodward, David F.

AU - Wang, Jenny W.

AU - Coleman, Robert A.

AU - Woodrooffe, Amanda J.

AU - Clark, Kenneth L.

AU - Stamer, W. Daniel

AU - Tao, Guoxian

AU - Fan, Shan

AU - Toris, Carol B.

PY - 2019/6

Y1 - 2019/6

N2 - 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.

AB - 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.

KW - EP receptor agonist

KW - glaucoma animal model

KW - pharmacology

UR - http://www.scopus.com/inward/record.url?scp=85066984047&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066984047&partnerID=8YFLogxK

U2 - 10.1089/jop.2018.0126

DO - 10.1089/jop.2018.0126

M3 - Article

C2 - 31025909

AN - SCOPUS:85066984047

VL - 35

SP - 265

EP - 277

JO - Journal of Ocular Pharmacology and Therapeutics

JF - Journal of Ocular Pharmacology and Therapeutics

SN - 1080-7683

IS - 5

ER -