The standard method used to determine the potency of antihistaminesis to assess the degree of suppression of skin response to histamine challenge.
The aims of this study were to compare the efficacy of 3 antihistaminesusing a histamine challenge test and the usefulness of on-site evaluation with that of photographic evaluation of skin-test reactions.
In this prospective, double-blind, crossover study, healthy volunteerswere given cetirizine 5 mg (CTZ-5) and 10 mg (CTZ-10), loratadine 10 mg (LOR), fexofenadine 60 mg BID (FEX), and placebo (PLC), in a randomly assigned order, with an interval of at least 1 week between treatments. Before and 0.5 to 24 hours after administration, the areas of flare and wheal induced by histamine iontophoresis were measured directly (on site) by 1 evaluator and by another evaluator using photographic images on a computer monitor.
Ten healthy volunteers (6 men, 4 women; mean age, 28.2 years[range, 20–39 years]; mean weight, 60.7 kg [range, 41–81 kg]) were enrolled. The data from 9 subjects were analyzed; the data from 1 subject were omitted because the subject used an over-the-counter cold medication containing diphenhydramine several times during the study. By both methods, all antihistamines were shown to suppress flare significantly from 4 to 24 hours after administration. CTZ was most potent in suppressing both flare and wheal. For flare, the areas as measured using on-site evaluation were larger overall than those measured using photographic evaluation, but the shapes of the time-course graphs were similar for both. Overall, the flare area measurements started to decrease significantly from baseline values 4 hours after drug administration, reached a nadir at 10.5 hours, and remained significantly lower compared with baseline values at 24 hours. Comparisons between antihistamines showed significant differences in mean flare areas between the 2 doses of CTZ and LOR from 8 to 12 hours after administration in both evaluation methods. The wheal areas were significantly reduced from baseline values by most of the antihistamines 4 to 12 hours after drug administration, reached their lowest values at 10.5 hours, and returned to near-baseline values at 24 hours. Comparisons with PLC values at each time point, however, showed significant differences only for CTZ-5 and CTZ-10 from 4 to 12 hours after administration. Comparison between antihistamines showed significant differences in mean flare areas between the 2 doses of CTZ and LOR from 8 to 12 hours after administration in both evaluation methods. Although the flare areas measured by both methods correlated linearly (r = 0.90; P < 0.001), the correlation for wheal areas was weaker (r = 0.76; P < 0.001).
In this study in healthy volunteers, single doses of CTZ 5 mg and CTZ 10 mg were more potent compared with single-dose LOR 10 mg and FEX 60 mg BID in suppressing skin response. Although linear correlations were found between skin-response areas, as measured by on-site and photographic evaluation, it was difficult to differentiate between wheal and flare by photographic evaluation, especially when a typical wheal was suppressed to slightly edematous erythema by antihistamines.