Effect of cetirizine, levocetirizine, and dextrocetirizine on histamine‐induced nasal response in healthy adult volunteers

Background: Cetirizine, an effective H 1 ‐receptor antagonist, is a racemate mixture of two enantiomers: levocetirizine ( R enantiomer) and dextrocetirizine ( S enantiomer). Methods: To investigate the pharmacologic activity of the two enantiomers of cetirizine, we conducted a randomized, double‐blind, four‐way, crossover study to assess the effect of treatment with 5 mg levocetirizine, 5 mg dextrocetirizine, and 10 mg cetirizine and matched placebo, on histamine‐induced changes in the nasal airways of 24 healthy volunteers. Four hours after a single oral intake, all subjects were challenged by nasal aerosol application with increasing doubling concentrations (from 0.25 to 32 mg/ml) of histamine in both nostrils. Nasal resistance was measured by passive anterior rhinomanometry (PAR), and changes in histamine threshold were calculated together with the absolute number of sneezes after each challenge. Results: Both levocetirizine and cetirizine significantly attenuated the histamine‐induced increase in nasal airway resistance by nearly 50% (from a median resistance of 2.51 Pa per cm 3 /s to 1.29 and 1.31 Pa per cm 3 /s, respectively) at the maximal concentration, and they concomitantly increased the histamine threshold by fourfold (from 8 to 32 mg/ml), compared with placebo. Sneezing was also attenuated by both levocetirizine and cetirizine. However, these antihistaminic effects were not seen with dextrocetirizine. Conclusions: This study shows a similar activity of levocetirizine and cetirizine on the inhibition of histamine‐induced increase in nasal resistance, indicating that the antihistaminic properties of cetirizine are probably attributable to levocetirizine.