loteprednol-etabonate and Hypersensitivity

Allergic conditions contribute significantly to the burden of chronic disease in the industrialized world. The increasing prevalence has lead research into the discovery and development of various new therapeutic strategies. Despite considerable efforts of the pharmaceutical industry, the leukotriene antagonists were the only new class of asthma treatments to be licensed in the past 30 years. Topical glucocorticoids (GCs) are the most potent and effective therapy for treating allergic diseases. However, their use is limited by diverse undesired effects. Changes in pharmacokinetic parameters of GCs may be an interesting and promising approach to improve efficacy and safety of inhaled GCs. Loteprednol etabonate has been developed on the basis of the retrometabolic drug design. In animal studies, it has been demonstrated to have long-lasting anti-allergic (anti-asthmatic) effects without influencing the hypothalamic-pituitary axis (HPA). This soft steroid is now in phase III of the clinical development. Recently, loteprednol has been proven to be effective in the management of allergic rhinitis (400 microg once daily). No suppression of HPA was observed at clinically effective and higher doses. In conclusion, loteprednol as the first representative of soft steroids elicits marked anti-inflammatory effects, but has no impact on endocrine responses. It may represent a promising new therapy in the treatment of allergic rhinitis and asthma.

Topics: Anaphylaxis; Androstadienes; Animals; Anti-Allergic Agents; Anti-Asthmatic Agents; Bronchoalveolar Lavage Fluid; Drug Design; Eosinophils; Glucocorticoids; Guinea Pigs; Hypersensitivity; Hypothalamo-Hypophyseal System; Loteprednol Etabonate; Male; Rats; Rats, Inbred BN

Loteprednol etabonate is a novel site-active corticosteroid synthesized through structural modifications of prednisolone-related compounds so that it will undergo a predictable transformation to an inactive metabolite. In double-masked studies, loteprednol etabonate was effective in the treatment of giant papillary conjunctivitis, seasonal allergic conjunctivitis, postoperative inflammation, and uveitis. The objective of this analysis was to determine the incidence of clinically significant elevations in intraocular pressure (IOP) with long-term use of loteprednol etabonate.. All subjects (healthy volunteers or patients with inflammation or allergy) in all sponsored loteprednol etabonate studies in the United States were evaluated. A clinically significant elevation in IOP was defined as > or = 10 mmHg at any visit, and long-term use was defined as > or = 28 days. Of the 2,210 subjects, 1,648 were treated for 28 days or longer with loteprednol etabonate (0.2% or 0.5%), prednisolone acetate 1%, or vehicle.. IOP elevation > or = 10 mmHg occurred in 1.7% (15/901) of patients taking long-term loteprednol etabonate, 0.5% (3/583) of those taking vehicle, and 6.7% (11/164) of those taking prednisolone acetate. Excluding patients who wore contact lenses, the incidence was 0.6% (4/624), 1.0% (3/304), and 6.7% (11/164) for loteprednol etabonate, vehicle, and prednisolone acetate, respectively. The incidence of IOP elevations with 0.2% loteprednol etabonate was 0.8% (1/133), similar to that for vehicle (0.7%, 1/135).. The results of this analysis in a large population of subjects undergoing long-term therapy and of a previously published controlled, double-masked study in corticosteroid responders suggest that loteprednol etabonate has less propensity to cause clinically significant elevations in IOP than prednisolone acetate.

Topics: Androstadienes; Anti-Inflammatory Agents; Clinical Trials as Topic; Humans; Hypersensitivity; Inflammation; Intraocular Pressure; Loteprednol Etabonate; Prednisolone; Reference Values; Time Factors