Predicting and Establishing the Clinical Efficacy of a Histamine H1-Receptor AntagonistDesloratadine, the Model Paradigm

Antihistamines are well established as a mainstay for treating allergic diseases, including seasonal and perennial allergic rhinitis as well as other conditions, such as chronic idiopathic urticaria. The development of new antihistamines is a multistage process that includes in vitro and in vivo assessments of the antihistaminic, anti-inflammatory and antiallergic properties of new therapies. Results of these assessments are critical for predicting and establishing the clinical efficacy of an antihistamine. The focus of this article is to review the investigational methods used to assess the efficacy, safety and tolerability of newer histamine H1-receptor antagonists. Desloratadine, a new-generation H1-receptor antagonist, was chosen to illustrate the use of this model paradigm. Data obtained from two large observational studies are presented, confirming results obtained from clinical trials that the in vitro inhibition of release of inflammatory mediators such as histamine, prostaglandins, leukotrienes and the reduction of secretion of cytokines such as IL-4 and IL-13 at physiological concentrations is reflected in increased efficacy, particularly upon nasal obstruction. A recent discovery that des- loratadine inhibits nuclear factor-κB may be the underlying explanation for much of this extra anti-inflammatory activity.