Inhibitory Effect of Ketotifen Transdermal Patch, A Novel Ophthalmic Formulation of Ketotifen, on Histamine-Induced Conjunctival Edema in Guinea Pigs

Abstract

Purpose: : Ketotifen patch (KT patch) is a newly formulated transdermal drug for the treatment of allergic conjunctivitis. KT patch is applied onto the eyelid and delivers ketotifen to conjunctiva continuously via skin. The effects of KT patch were pharmacologically observed in comparison with those of ketotifen 0.025% ophthalmic solution (KT solution) on histamine-induced conjunctival edema in guinea pigs.

Methods: : Male Hartley guinea pigs (6 weeks old) were used in strict accordance with the ARVO statement. Evans blue (EB, 20 mg/kg) was intravenously administered and histamine (His, 0.1mg) was injected into the lower palpebral conjunctiva under general anesthesia. After 30 min, the guinea pigs were euthanized, and the lower conjunctiva and the eyelid were dissected. Conjunctival vascular leakage, the amount of EB extracted from each dissected tissue, was determined for evaluating conjunctival edema. In a dose-response study, KT patch (0.1% - 6%) was applied for 8 hrs and removed at 16 hrs before the His injection. In a duration of action study, KT 4% patch was applied for 4 or 8 hrs and removed at 0, 8 or 16 hrs before the His injection, and KT solution was instilled 5 min or 1, 8 or 16 hrs before the His injection, respectively.

Results: : KT patch dose-dependently inhibited His-induced vascular leakage. When KT 4% patch was applied for 8 hrs, it showed a significant inhibition at 0 hr (67.1%), 8 hrs (57.4%) and 16 hrs (63.0%) after its removal respectively, and also the patch applied for 4 hrs significantly inhibited the leakage (59.2%). KT solution significantly inhibited the leakage at 1 hr (78.1%), but it did not at 8 and 16 hrs after instillation.

Conclusions: : The effects of KT patch were potent and long-lasting compared with KT solution on a His-induced conjunctival edema model. This unique transdermal patch may be very useful therapeutic alternative in treating allergic conjunctivitis.

Keywords: conjunctivitis • eyelid