Ocular hypotensive efficacy, safety and systemic absorption of AR-12286 ophthalmic solution in normal volunteers

British Journal of Ophthalmology

Volumn 97, Issue 5, 2013, Pages 567-572

  Kopczynski, Casey ^a   Novack, Gary D ^b   Swearingen, Dennis ^c   Van Haarlem, Thomas ^a  

^a and Durham   (United States)

^b PHARMALOGIC DEVELOPMENT INC   (United States)

^c CELERION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AR 12286; AR 12468; DRUG METABOLITE; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ADULT; AREA UNDER THE CURVE; ARTICLE; ASTHENOPIA; BLURRED VISION; BURNING SENSATION; CONJUNCTIVAL HYPEREMIA; CONNECTIVE TISSUE DISEASE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DOSAGE FORM COMPARISON; DRUG EFFICACY; DRUG EXPOSURE; DRUG FORMULATION; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; DRY THROAT; EYE DISEASE; EYE IRRITATION; FEMALE; GASTROINTESTINAL SYMPTOM; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; INSTILLATION SITE IRRITATION; INTRAOCULAR HYPERTENSION; INTRAOCULAR PRESSURE; LACRIMATION DISORDER; MALE; MAXIMUM PLASMA CONCENTRATION; MEDIASTINUM DISEASE; MORNING DOSAGE; MUSCULOSKELETAL DISEASE; NECK PAIN; NEUROLOGIC DISEASE; OROPHARYNX PAIN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY TRACT DISEASE; SKIN DISEASE; TANDEM MASS SPECTROMETRY; THORAX DISEASE; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT DURATION; VESSEL PUNCTURE SITE PAIN; VOLUNTEER;

ABSORPTION; ADULT; ANTIHYPERTENSIVE AGENTS; BIOLOGICAL AVAILABILITY; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; ENZYME INHIBITORS; FEMALE; HUMANS; INTRAOCULAR PRESSURE; ISOQUINOLINES; MALE; MICROSCOPY; MIDDLE AGED; OPHTHALMIC SOLUTIONS; OPHTHALMOSCOPY; RHO-ASSOCIATED KINASES; TANDEM MASS SPECTROMETRY; TONOMETRY, OCULAR; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84876283378     PISSN: 00071161     EISSN: 14682079     Source Type: Journal    
DOI: 10.1136/bjophthalmol-2012-302466     Document Type: Article

References (22)

1. American Academy of Ophthalmology Glaucoma Panel. Preferred Practice Pattern: Primary Open-Angle Glaucoma. 2010. San Francisco, CA, American Academy of Ophthalmology
2. American Academy of Ophthalmology Glaucoma Panel. Preferred Practice Pattern: Primary Open-Angle Gla ucoma Suspect. 2010. San Francisco, CA, American Academy of Ophthalmology
3. European Glaucoma Society. Terminology and guidelines for glaucoma. 3rd edn. 2008
4. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the early manifest glaucoma trial. Arch Ophthalmol 2002;120:1268-79
5. Kass MA, Heuer DK, Higginbotham EJ, et al. The ocular hypertension treatment study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch.Ophthalmol 2002;120:701-1 3
6. AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol 2000;130:429-40
7. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the collaborative initial glaucoma treatment study comparing initial treatment randomized to medications or surgery. Ophthalmology 2001 ;108:1943-53
8. Tian B, Kaufman PL. Effects of the Rho kinase inhibitor Y-27632 and the phosphatase inhibitor calyculin A on outflow facility in monkeys. Exp Eye Res 2005;80:215-25
9. Tokushige H,Inatani M,Nemoto S,et al. Effects of topical administration of Y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys. Invest Ophthalmol Vis Sci. 2007. 48.3216-22
10. Honjo M, Tanihara H, Inatani M, et al. Effects of rho-associated protein kinase inhibitor Y-27632 on intraocular pressure and outflow facility. Invest Ophthalmol Vis Sci 2001;42:137-44
11. Rao PV, Deng PF, Kumar J, et al. Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632. Invest Ophthalmol Vis Sci 2001;42:1029-37
12. Brubaker RF. Targeting outflow facility in glaucoma management. Survey Ophthalmol 2003;48(Suppl 1):S17-20
13. deLong MA, Sturdivant JM, Royalty SM, et al. Discovery and in vitro SAR of AR-12286, a Potent Kinase Inhibitor for the Treatment of Glaucoma. ARVO Meeting Abstracts 2009;50:ARVO E-Abstract 4058
14. Wang RF, Serle JB, Kopczynski C. Effect of 0.6% AR-12286 on a queous humor dynamics in 6 normotensive monkey eyes. ARVO Meeting Abstracts 2009;50:ARVO E-abstract 1465
15. Williams RD, Novack GD, van Haarlem T, et al. Ocular hypotensive effect of the Rho kinase in hibitor AR-12286 in patients with glaucoma and ocular hypertension. Am J Ophthalmol 2011;152:834-41
16. Stone JL, Robin AL, Novack GD, et al. An objective evaluation of eye-drop instillation in glaucoma patients. Arch Ophthalmol 2009;127:732-6
17. Sherwood MB, Craven ER, Chou C, et al. Twice-daily 0.2% brimonidine-0.5% timolol fixed-combination therapy vs monotherapy with timolol or b rimonidine in patients with glaucoma or ocular hypertension: a 12-month randomized trial. Arch Ophthalmol 2006;124:1230-8
18. Uehata M, Ishizaki T, Satoh H, et al. Calcium sensitization of smoot h muscle mediated by a Rho-associated protein kinase in hypertension. Nature 1997;389:990-4
19. Sabanay I, Gabelt BT, Tian B, et al. H-7 effects on the structure and fluid conductance of monkey trabecular meshwork. Arch Ophthalmol 2000;118:955-62
20. Tanihara H, Inatani M, Honjo M, et al. Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inh ibitor, SNJ-1656, in healthy volunteers. Arch Ophthalmol 2008;126:309-15
21. Novack GD, Lue JC, Duzman E. Power estimates in designing glaucoma trials. Glaucoma 1989;11:166-8
22. Lim KS, Nau CB, O'Byrne MM, et al. Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study. Ophthalmology 2008;115:790-5.