Duration of Action of Topical Anti–Allergy Drugs in a Guinea Pig Model of Histamine–Induced Conjunctival Vascular Permeability

Abstract

Purpose: : Topical application of 0.1% olopatadine has been shown to provide significant attenuation of histamine–induced conjunctival vascular permeability within five minutes and for as long as twenty–four hours following topical administration. The duration of action of olopatadine was compared to that of epinastine, emedastine, levocabastine, azelastine, and ketotifen.

Methods: : Male Hartley outbred guinea pigs (250–300 g) were administered drug or vehicle as single O.D. topical drops at times ranging from 30 min to 24 hrs prior to histamine challenge. One hour prior to histamine challenge, the animals were administered 1 ml Evans blue dye (1 mg/ml) via the marginal ear vein. Histamine (300 ng) was administered via subconjunctival injection and the guinea pigs were sacrificed 30 min later. Conjunctival vascular permeability was assessed as the area and color intensity stained with Evans blue dye. The potencies of each drug were determined by calculating an ED₅₀ for inhibition of vascular leakage compared to vehicle treatment at each time point.

Results: : Olopatadine was the only compound tested that was significantly effective sixteen hours following a single topical application. The ED₅₀ for olopatadine at sixteen hours was 0.031%, which is almost an order of magnitude less than the concentration of 0.1% contained in the ophthalmic product Patanol. While not significantly effective at sixteen hours, levocabastine (ED₅₀ = 0.046%) and ketotifen (ED₅₀ = 0.027%) had significant inhibitory activity for up to 8 hrs. Epinastine (ED₅₀ = 0.02%), emedastine (ED₅₀ = 0.019%), and azelastine (ED₅₀ < 0.05%) were only significantly effective for up to 4 hrs.

Conclusions: : Olopatadine exhibited the longest duration of action for inhibition of histamine–induced vascular permeability in guinea pigs of any topical anti–allergic drug currently marketed for ophthalmic use. Concentrations of olopatadine which provided greater than 50% inhibition of the histamine–induced vascular response were consistently less than 0.1% throughout a sixteen hour duration. Olopatadine was the only drug tested which was significantly effective over the 16 hour time period at concentrations relevant to those used in marketed ophthalmic products.

Keywords: pharmacology • conjunctiva