loteprednol-etabonate and Rhinitis--Allergic--Seasonal

Seasonal allergic conjunctivitis (SAC) is an inflammatory response of the conjunctiva triggered by exposure to seasonal allergens. Treatment options for SAC include artificial tears, antihistamines, decongestants, mast cell stabilizers, nonsteroidal anti-inflammatory drugs, dual antihistamine/mast cell stabilizers, immunotherapy and corticosteroids. Topical, intranasal and systemic formulations of corticosteroids have traditionally provided the most effective relief of the inflammation and signs and symptoms associated with severe, acute exacerbations of SAC. However, steroid-induced ocular and systemic side-effects have limited the prescribing of these agents. This limitation of traditional corticosteroids led to the development of modified corticosteroids that retain the anti-inflammatory mechanism of action of traditional corticosteroids with a much-improved safety profile because of their rapid breakdown to inactive metabolites after exerting their activity. The development of one such novel corticosteroid, loteprednol etabonate (LE), led to the insertion of an ester (instead of a ketone) group at the carbon-20 (C-20) position of the basic corticosteroid structure. Clinical trials assessing this C-20 ester corticosteroid have demonstrated similar efficacy to C-20 ketone corticosteroids in the prevention or treatment of the signs and symptoms of SAC but with a greatly improved safety profile, as the C-20 ester corticosteroid is less likely to elevate intraocular pressure. In addition, the ketone at the C-20 position has been implicated in the formation of cataract, while nonketolic corticosteroids do not form Schiff base intermediates with lens proteins, which is a common first step in cataractogenesis. The clinical relevance of the C-20 ester corticosteroid class, as modelled by LE, is that they provide both effective and safe treatment of the inflammation associated with SAC and relief of its signs and symptoms. Loteprednol etabonate offers a well-tolerated treatment option for patients with debilitating acute exacerbations as well as chronic forms of the disease.

Topics: Androstadienes; Anti-Allergic Agents; Conjunctivitis, Allergic; Glucocorticoids; Humans; Loteprednol Etabonate; Practice Guidelines as Topic; Rhinitis, Allergic, Seasonal; Seasons

Loteprednol etabonate (LE) is a novel soft steroid that was designed to improve the benefit/risk ratio of topical corticosteroid therapy. This study assesses the clinical efficacy and safety of three different doses of LE nasal spray in seasonal allergic rhinitis (SAR).. In this single-center, double-blind, placebo-controlled, parallel-group trial 165 subjects with SAR to grass pollen received daily single doses of either 100, 200, 400 microg LE nasal spray, or placebo for 14 days. The patients underwent three 4-h allergen challenges with grass pollen in an environmental exposure unit at a screening visit (baseline) and on days 7 and 14 of treatment. Standardized nasal symptom scores were obtained every 20 min. Nasal flow, nasal secretions, and FEV(1) were measured every hour during allergen challenges.. After 14 days of treatment, patients who received 400 microg LE had significantly lower total nasal symptom scores compared with those receiving placebo (P = 0.007). LE400 reduced rhinorrhea, nasal congestion, nasal itching, the amount of nasal secretions, and improved nasal flow as compared with placebo (P < 0.05). LE100 and LE200 were not significantly different from placebo. All treatments were well tolerated.. Loteprednol 400 microg once daily is superior to placebo and the only effective dose tested in improving nasal symptoms and objective parameters in patients with SAR.

Topics: Administration, Intranasal; Adult; Aerosols; Allergens; Androstadienes; Anti-Allergic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Environmental Exposure; Female; Humans; Loteprednol Etabonate; Male; Middle Aged; Rhinitis, Allergic, Seasonal; Suspensions; Treatment Outcome