Assessment of antihistamine efficacy and potency

H-1 antihistamines are widely used in the treatment of conditions such as s easonal and perennial allergic rhinitis, urticaria and angioedema, as well as being an adjunct therapy for anaphylaxis. The development of new compoun ds within this class of pharmacological agents is based on preclinical and clinical assessments prior to registration. Preclinical assessment of novel compounds has been advanced both by the def inition of the molecular structure of the H-1 receptor and by high throughp ut screening, which allows the definition of potent and selective candidate compounds. The elimination, in subsequent evaluations, of those compounds with potential for central nervous system and cardiotoxic effects and those with inappropriate pharmacokinetics restricts the subsequent toxicological and clinical evaluation of novel H-1 antihistamines. Clinical evaluation i s based initially on human volunteer studies to define pharmacodynamic, pha rmacokinetic and safety parameters. Local challenge models such as in the s kin or nose for oral therapy or nose and conjunctiva for topical drug devel opment allow definition of potential dose for administration, speed of onse t of activity and duration of effect, both in comparison to placebo and to reference compounds. While a range of laboratory allergen challenge models, pollen chamber challenge studies and acute 'day in the park' study designs have been used in the early clinical evaluation of H-1 antihistaminic acti vity, ultimately it is the efficacy of novel compounds in naturally occurri ng disease that is of importance. The assessment of the magnitude and profi le of clinical disease improvement in specific disease areas is thus the cr ucial evaluation. The appropriate selection and characterization of patient s, the optimization of the trial design, dependent upon the nature of the d isease, and the appropriate selection of endpoints for analysis are thus cr itical considerations, as well as evaluation of appropriate safety criteria .