The non-sedating antihistamines show a diversity of fates in the body and the parent drugs and metabolites may differ in their biological properties. Clinically significant interactions with inhibitors of cytochrome P450 have been reported primarily for terfenadine, which has the potential for cardiac toxicity, and is metabolized to fexofenadine, an antihistamine without cardiac effects. Astemizole shares many of these characteristics and important safety-related interactions are likely. Loratadine undergoes extensive metabolism so that pharmacokinetic interactions could occur, but they would be of little clinical importance because of the lack of cardiac activity of the parent drug and its metabolites. Ebastine also undergoes pharmacokinetic interactions, the significance of which is dependent on clarification of the extent of any relevant cardiotoxicity of both ebastine and its metabolite. Interactions would not be clinically important for cetirizine and fexofenadine which do not show cardiac effects and are eliminated with little metabolism.