title: Duration of action of topical antiallergy drugs in a Guinea pig model of histamine-induced conjunctival vascular permeability.
abstract: The topical application of 0.1% olopatadine has been shown to provide significant attenuation of histamine-induced conjunctival vascular permeability (CVP) within 5 min and for as long as 24 h following a topical administration. The duration of the action of olopatadine was compared to that of epinastine, azelastine, and ketotifen. Male Hartley outbred guinea pigs (weighing 250-300 g) were administered a drug or vehicle as single O.D. topical drops, at times ranging from 4 to 24 h prior to histamine challenge. One (1) h prior to histamine challenge, the animals were administered 1 mL of Evans blue dye (1 mg/mL) through the marginal ear vein. Histamine (300 ng) was administered by a subconjunctival injection, and the guinea pigs were sacrificed 30 min later. CVP was assessed as the area and color intensity stained with Evans blue dye. The potencies of each drug were determined by calculating a 50% effective dose (ED(50)) for the inhibition of vascular leakage, compared to vehicle treatment, at each time point. Olopatadine was the only compound tested that was significantly effective 16 h following a single topical application. The ED(50) for olopatadine at 16 h was 0.031%. Epinastine, azelastine, and ketotifen were only significantly effective for up to 4 h. Olopatadine exhibited the longest duration of action for inhibition of histamine-induced vascular permeability in guinea pigs of any topical antiallergic drug tested. Concentrations of olopatadine, which provided a greater than 50% inhibition of the histamine-induced vascular response, were consistently less than 0.1% over a 16-h pretreatment interval.
authors.affiliation: External Disease Research, Ophthalmology Discovery, Alcon Research, Ltd., Fort Worth, TX, USA. clay.beauregard@alconlabs.com
authors.forename: Clay
authors.initials: C
authors.lastname: Beauregard
authors.forename: Donna
authors.initials: D
authors.lastname: Stephens
authors.forename: Leighann
authors.initials: L
authors.lastname: Roberts
authors.forename: Daniel
authors.initials: D
authors.lastname: Gamache
authors.forename: John
authors.initials: J
authors.lastname: Yanni
mesh_terms: D000287:Administration, Topical; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002199:Capillary Permeability / Q000187:drug effects*; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism; D003692:Delayed-Action Preparations; D003984:Dibenzazepines / Q000008:administration & dosage / Q000493:pharmacokinetics; D003990:Dibenzoxepins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D007665:Ketotifen / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D000069605:Olopatadine Hydrochloride; D009883:Ophthalmic Solutions; D010793:Phthalazines / Q000008:administration & dosage / Q000493:pharmacokinetics