Therapeutic index of H1-antihistamines: example of cetirizine

The second generation H1 antihistamines were considered to have an improved risk/benefit ratio because of their low penetration into the brain and their very low incidence of CNS depressant effects. Nevertheless, the cardiac rhythm disturbances described under terfenadine and astemizole intake drew the attention to the fact that the low penetration into the brain is only one limited item in the evaluation of their respective therapeutic indices. A correct evaluation of the therapeutic index should always comprise a large series of items: all desired and not desired effects and properties should be considered together with the physicobiochemical mechanisms of the drugs at cell and membrane levels.