title: The role of platelet activating factor and the efficacy of apafant ophthalmic solution in experimental allergic conjunctivitis.
abstract: Platelet-activating factor (PAF) may be an important mediator in allergic conjunctivitis. In this study, apafant, a potent PAF antagonist, was evaluated for topical ocular anti-PAF activity in PAF and antigen stimulated conjunctivitis models. PAF, when injected into parpebral conjunctiva, provoked an acute increase, measured as dye leakage, in conjunctival vascular permeability. Apafant inhibited this response in a dose-related manner, and the inhibitory action of 0.1% apafant lasted for at least 6 hours duration. PAF, when instilled into the conjunctival sac, induced itch-scratching behavior and clinical symptoms, such as conjunctival redness and edema. These were inhibited by pretreatment with apafant ophthalmic solution. In a passive conjunctival anaphylaxis model in guinea pigs, significant inhibition of the allergic response was observed following topical ocular administration of apafant 5 and 15 minutes prior to the antigen challenge. We have demonstrated that PAF plays an important role in the development of allergic conjunctivitis. These results clearly indicate that apafant has potential as a topical ocular anti-PAF for treating allergic conjunctivitis.
authors.affiliation: Research & Development Division, Santen Pharmaceutical Co, Ltd, Nara, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Kato
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Kurose
authors.forename: Tomoko
authors.initials: T
authors.lastname: Oda
authors.forename: Suguru
authors.initials: S
authors.lastname: Miyaji
mesh_terms: D000818:Animals; D000941:Antigens / Q000009:adverse effects / Q000276:immunology; D001381:Azepines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002199:Capillary Permeability / Q000187:drug effects* / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000139:chemically induced* / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004395:Dye Dilution Technique; D006168:Guinea Pigs; D006801:Humans; D007116:Immunization, Passive; D007665:Ketotifen / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D009883:Ophthalmic Solutions; D010972:Platelet Activating Factor / Q000009:adverse effects*; D011537:Pruritus / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000941:Antigens; D001381:Azepines; D009883:Ophthalmic Solutions; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D007665:Ketotifen