Pharmacological, Pharmacokinetic and Clinical Properties of Olopatadine Hydrochloride, a New Antiallergic Drug

Abstract

ABSTRACT-Olopatadine hydrochloride (olopatadine, 11-[(Z)-3-(dimethylamino)propylidene]-6,11-dihydrodibenz [b,e]oxepin-2-acetic acid monohydrochloride) is a novel antiallergic/ histamine H 1 -receptor antagonistic drug that was synthesized and evaluated in our laboratories. Oral administration of olopatadine at doses of 0.03 mg/ kg or higher inhibited the symptoms of experimental allergic skin responses, rhinoconjunctivitis and bronchial asthma in sensitized guinea pigs and rats. Olopatadine is a selective histamine H 1 -receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig ventricular myocytes, myocardium and human ether-a-go-go-related gene channel. Olopatadine was highly and rapidly absorbed in healthy human volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was considerably low in the clearance of olopatadine in humans. Olopatadine is one of the few renal clearance drugs in antiallergic drugs. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritis cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. Ophthalmic solution of olopatadine was also approved in the United States for the treatment of seasonal allergic conjunctivitis in December, 1996 (Appendix: also in the European Union, it was approved in February 2002).

Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

“…In an epicutaneous allergen challenge murine AD model, treatment with the selective H1R antihistamine, olopatadine, not only suppressed inflammation and scratching by inhibiting cytokine/chemokine production (e.g., IL-31, TSLP, TARC) but also improved the skin barrier function [65,66,67,68,69]. Olopatadine has inhibitory effects on the release of inflammatory mediators (e.g., histamine, leukotriene, thromboxane, and tachykinins), which could explain these broad anti-allergic properties [70]. Olopatadine was approved in 2000 in Japan for the treatment of several conditions including AD, chronic urticaria, and allergic rhinitis.…”

Comparison of efficacy, safety, and cost-effectiveness of rupatadine and olopatadine in patients of allergic rhinitis: A prospective, randomized, double-blind, parallel group study

“…Olopatadine can reduce the amount of cell-associated PAF by 52.8%, which is more than rupatadine. [11] PAF known to increase vascular permeability and is increasingly recognized as an important mediator in inflammation. It also suppresses LTs and TxA2 release, and PAF formation by reducing arachidonic acid release from membrane phospholipids, probably through interference with phospholipase A2.…”

Comparison of the Efficacy of Olopatadine and Fexofenadine in Chronic Idiopathic Urticaria Patients: A Crossover Study

“…Olopatadine is known to exhibit inhibitory effects on the release of inflammatory lipid mediators, such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils [5]. Whereas several trials compared the efficacy of second-generation H 1 antihistamines on CIU [6,7,8], no study has directly compared the clinical efficacy of olopatadine to that of other H 1 antihistamines in patients with CIU.…”