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

Background: Cetirizine, an effective Hi-receptor antagonist, is a racemate mixture of two enantiomers: levocetirizine (R enantiomer) and dextrocetiriz ine (S enantiomer). Methods: To investigate the pharmacologic activity of the two enantiomers o f cetirizine, we conducted a randomized, double-blind, four-way, crossover study to assess the effect of treatment with 5 mg levocetirizine, 5 mg dext rocetirizine, and 10 mg cetirizine and matched placebo, on histamine-induce d changes in the nasal airways of 24 healthy volunteers. Four hours after a single oral intake, all subjects were challenged by nasal aerosol applicat ion with increasing doubling concentrations (from 0.25 to 32 mg/ml) of hist amine in both nostrils. Nasal resistance was measured by passive anterior r hinomanometry (PAR), and changes in histamine threshold were calculated tog ether with the absolute number of sneezes after each challenge. Results: Both levocetirizine and cetirizine significantly attenuated the hi stamine-induced increase in nasal airway resistance by nearly 50% (from a m edian resistance of 2.51 Pa per cm(3)/s to 1.29 and 1.31 Pa per cm3/s, resp ectively) at the maximal concentration, and they concomitantly increased th e histamine threshold by fourfold (from 8 to 32 mg/ml), compared with place bo. Sneezing was also attenuated by both levocetirizine and cetirizine. How ever, these antihistaminic effects were not seen with dextrocetirizine. Conclusions: This study shows a similar activity of levocetirizine and ceti rizine on the inhibition of histamine-induced increase in nasal resistance, indicating that the antihistaminic properties of cetirizine are probably a ttributable to levocetirizine.