Ocular pharmacokinetics and hypotensive activity of PF-04475270, an EP4 prostaglandin agonist in preclinical models

Experimental Eye Research

Volumn 89, Issue 5, 2009, Pages 608-617

  Prasanna, Ganesh ^a   Fortner, Jay ^a   Xiang, Cathie ^a   Zhang, Eric ^a   Carreiro, Samantha ^a   Anderson, Scott ^a   Sartnurak, Soisurin ^a   Wu, Grace ^a   Gukasyan, Hovhannes ^a   Niesman, Michael ^a   Nair, Sajiv ^a   Rui, Eugene ^a   Lafontaine, Jennifer ^a   Almaden, Chau Doan ^a   Wells, Peter ^a   Krauss, Achim ^a  

^a PFIZER INC   (United States)

Author keywords

dog; glaucoma; intraocular pressure; PF 04475270; pharmacokinetics; prostaglandin EP4

Indexed keywords

BETA LACTAMASE; CP 734432; PF 04475270; PROSTAGLANDIN E RECEPTOR; PROSTAGLANDIN E RECEPTOR 4; PROSTAGLANDIN RECEPTOR STIMULATING AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIHYPERTENSIVE ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CONJUNCTIVAL HYPEREMIA; CONTROLLED STUDY; CORNEA EPITHELIUM; CORNEA PERMEABILITY; CYCLIC AMP RESPONSIVE ELEMENT; DOG; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG HYDROLYSIS; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG STRUCTURE; GLAUCOMA; HALF LIFE TIME; HUMAN; HUMAN CELL; INTRAOCULAR HYPERTENSION; INTRAOCULAR PRESSURE; MORNING DOSAGE; NONHUMAN; PHARMACODYNAMICS; PRIORITY JOURNAL; RABBIT; RECEPTOR AFFINITY; SINGLE DRUG DOSE;

ADMINISTRATION, TOPICAL; ANIMALS; BIOLOGICAL AVAILABILITY; CHO CELLS; CRICETINAE; CRICETULUS; CYCLIC AMP; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; EYE; HUMANS; HYDROLYSIS; HYPEREMIA; INTRAOCULAR PRESSURE; MODELS, ANIMAL; OPHTHALMIC SOLUTIONS; PERMEABILITY; PRODRUGS; PYRROLIDINONES; RABBITS; RECEPTORS, PROSTAGLANDIN E; THIOPHENES; TRANSFECTION;

EID: 70349464680     PISSN: 00144835     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.exer.2009.05.002     Document Type: Article

References (23)

1. Biswas S., Bhattacherjee P., and Paterson C.A. Prostaglandin e2 receptor subtypes, ep1, ep2, ep3 and ep4 in human and mouse ocular tissues-a comparative immunohistochemical study. Prostaglandins Leukot. Essent. Fatty Acids 71 (2004) 277-288
2. Breyer R.M., Bagdassarian C.K., Myers S.A., and Breyer M.D. Prostanoid receptors: subtypes and signaling. Annu. Rev. Pharmacol. Toxicol. 41 (2001) 661-690
3. Crider J.Y., and Sharif N.A. Functional pharmacological evidence for ep2 and ep4 prostanoid receptors in immortalized human trabecular meshwork and non-pigmented ciliary epithelial cells. J. Ocul. Pharmacol. Ther. 17 (2001) 35-46
4. Fujino H., West K.A., and Regan J.W. Phosphorylation of glycogen synthase kinase-3 and stimulation of t-cell factor signaling following activation of ep2 and ep4 prostanoid receptors by prostaglandin e2. J. Biol. Chem. 277 (2002) 2614-2619
5. Fujino H., Salvi S., and Regan J.W. Differential regulation of phosphorylation of the camp response element-binding protein after activation of ep2 and ep4 prostanoid receptors by prostaglandin e2. Mol. Pharmacol. 68 (2005) 251-259
6. Hristovska A.M., Rasmussen L.E., Hansen P.B., Nielsen S.S., Nusing R.M., Narumiya S., Vanhoutte P., Skott O., and Jensen B.L. Prostaglandin e2 induces vascular relaxation by e-prostanoid 4 receptor-mediated activation of endothelial nitric oxide synthase. Hypertension 50 (2007) 525-530
7. Ke H.Z., Crawford D.T., Qi H., Simmons H.A., Owen T.A., Paralkar V.M., Li M., Lu B., Grasser W.A., Cameron K.O., Lefker B.A., Dasilva-Jardine P., Scott D.O., Zhang Q., Tian X.Y., Jee W.S., Brown T.A., and Thompson D.D. A nonprostanoid ep4 receptor selective prostaglandin e2 agonist restores bone mass and strength in aged, ovariectomized rats. J. Bone Miner. Res. 21 (2006) 565-575
8. Labbe E., Lock L., Letamendia A., Gorska A.E., Gryfe R., Gallinger S., Moses H.L., and Attisano L. Transcriptional cooperation between the transforming growth factor-beta and wnt pathways in mammary and intestinal tumorigenesis. Cancer Res. 67 (2007) 75-84
9. Nakagawa K., Imai Y., Ohta Y., and Takaoka K. Prostaglandin e2 ep4 agonist (ono-4819) accelerates bmp-induced osteoblastic differentiation. Bone 41 (2007) 543-548
10. Nathanson J.A., and Mckee M. Alterations of ocular nitric oxide synthase in human glaucoma. Invest. Ophthalmol. Vis. Sci. 36 (1995) 1774-1784
11. Nathanson J.A., and Mckee M. Identification of an extensive system of nitric oxide-producing cells in the ciliary muscle and outflow pathway of the human eye. Invest. Ophthalmol. Vis. Sci. 36 (1995) 1765-1773
12. Nilsson S.F., Drecoll E., Lutjen-Drecoll E., Toris C.B., Krauss A.H., Kharlamb A., Nieves A., Guerra T., and Woodward D.F. The prostanoid ep2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey. Invest. Ophthalmol. Vis. Sci. 47 (2006) 4042-4049
13. Nishigaki N., Negishi M., and Ichikawa A. Two gs-coupled prostaglandin e receptor subtypes, ep2 and ep4, differ in desensitization and sensitivity to the metabolic inactivation of the agonist. Mol. Pharmacol. 50 (1996) 1031-1037
14. Regan J.W. Ep2 and ep4 prostanoid receptor signaling. Life Sci. 74 (2003) 143-153
15. Sakamoto A., Matsumura J., Mii S., Gotoh Y., and Ogawa R. A prostaglandin e2 receptor subtype ep4 agonist attenuates cardiovascular depression in endotoxin shock by inhibiting inflammatory cytokines and nitric oxide production. Shock 22 (2004) 76-81
16. Schlotzer-Schrehardt U., Zenkel M., and Nusing R.M. Expression and localization of fp and ep prostanoid receptor subtypes in human ocular tissues. Invest. Ophthalmol. Vis. Sci. 43 (2002) 1475-1487
17. Sugimoto Y., and Narumiya S. Prostaglandin e receptors. J. Biol. Chem. 282 (2007) 11613-11617
18. Toris C.B., Camras C.B., Yablonski M.E., and Brubaker R.F. Effects of exogenous prostaglandins on aqueous humor dynamics and blood-aqueous barrier function. Surv. Ophthalmol. 41 Suppl. 2 (1997) S69-S75
19. Tripathi R.C., Li J., Chan W.F., and Tripathi B.J. Aqueous humor in glaucomatous eyes contains an increased level of tgf-beta 2. Exp. Eye Res. 59 (1994) 723-727
20. Wang W.H., Mcnatt L.G., Pang I.H., Millar J.C., Hellberg P.E., Hellberg M.H., Steely H.T., Rubin J.S., Fingert J.H., Sheffield V.C., Stone E.M., and Clark A.F. Increased expression of the wnt antagonist sfrp-1 in glaucoma elevates intraocular pressure. J. Clin. Invest. 118 (2008) 1056-1064
21. Woodward D.F., Bogardus A.M., Donello J.E., Fairbairn C.E., Gil D.W., Kedzie K.M., Burke J.A., Kharlamb A., Runde E., Andrews S.W., et al. Molecular characterization and ocular hypotensive properties of the prostanoid ep2 receptor. J. Ocul. Pharmacol. Ther. 11 (1995) 447-454
22. Woodward D.F., Nilsson S.F., Toris C.B., Kharlamb A.B., Nieves A.L., and Krauss A.H. Prostanoid EP4 receptor stimulation produces ocular hypotension by a mechanism that does not appear to involve uveoscleral outflow. Invest. Ophthalmol. Vis. Sci. (2009) Feb (Epub ahead of print)
23. Wordinger R.J., Fleenor D.L., Hellberg P.E., Pang I.H., Tovar T.O., Zode G.S., Fuller J.A., and Clark A.F. Effects of tgf-beta2, bmp-4, and gremlin in the trabecular meshwork: implications for glaucoma. Invest. Ophthalmol. Vis. Sci. 48 (2007) 1191-1200