Development of New H1 Antihistamines: The Importance of Pharmacokinetics in the Evaluation of Safe and Therapeutically Effective Agents

H1 antihistamines are widely used in the treatment of allergic disorders. The CNS depressant and antimuscarinic effects of the first generation compounds limited their use in allergic disorders, and the second generation compounds were developed to reduce or eliminate these effects. However, the use of the first second generation H1 antihistamines, terfenadine and astemizole, under certain circumstances, was associated with adverse cardiac effects, which were occasionally fatal and they were withdrawn from the market. This review examines the pharmacokinetics of the second generation antihistamines and the impact of the pharmacokinetic properties on their efficacy and safety, particularly with regard to their effects on the central nervous and cardiovascular systems and their potential for interactions with concomitantly administered drugs and dietary components.