Activity of ebastine (10 and 20 mg) and cetirizine at 24 hours of a steady state treatment in the skin of healthy volunteers.

We have compared the inhibitory effects of ebastine (10 mg), ebastine (20 mg) and cetirizine (10 mg) on histamine-induced wheal and flare skin reactions 24 h following a 6-day-long treatment. This was a double-blind, randomised, crossover, placebo-controlled study involving 24 healthy volunteers (18-65 years) with negative skin prick tests and the absence of specific IgEs to common allergens. Subjects were randomised to receive each of the following treatments once daily for 6 days: ebastine (10 mg), ebastine (20 mg), cetirizine (10 mg) or placebo with a washout period of 5 days. Twenty-four hours after the last dose of each treatment, histamine skin prick tests were performed (0, 0.5, 1, 2.5, 5, 10, 20, 50, 100 and 200 mg/mL), and wheal and flare responses were measured. All active treatments produced significant inhibition of the wheal responses compared to placebo (P < 0.001). Wheal response inhibition was significantly better with 20 mg of ebastine compared with 10 mg of ebastine and 10 mg of cetirizine. In a comparison to histamine concentrations required to produce a wheal surface area of 10 mm2, 20 mg of ebastine was also significantly better than ebastine 10 mg and cetirizine (P < 0.001), and 10 mg ebastine was significantly better than cetirizine (P < 0.05). Highly significant (P < 0.001) effects on the flare response were observed with each active treatment compared to placebo, with no difference between groups. The frequency of adverse events, primarily somnolence, was similar among the four treatment groups. Our results clearly indicate that ebastine, at either recommended dosage of 10 and 20 mg, and cetirizine produced significant inhibition of the histamine-induced wheal and flare reaction compared to placebo for up to 24 h. A superior efficacy of 20 mg of ebastine is observed compared with 10 mg of ebastine and 10 mg of cetirizine on the skin wheal response 24 h after the last dose of a 6-day-long treatment. This study clearly proves ebastine to be an effective, truly once-daily antihistamine.

Consistency and efficacy of cetirizine (10 mg) versus ebastine (20 mg) at 4 h on skin reactivity.

OBJECTIVE: We compared the consistency and efficacy of the two antihistamines, cetirizine (10 mg) and ebastine (20 mg) on histamine skin reactivity 4 h after treatment. METHODS: Twenty-four healthy volunteers participated in a randomised double-blind cross-over study. The areas of wheals and flares induced by increasing (0, 5, 10, 50, 100, 200, 300 mg/ml) histamine concentrations, administered by prick tests, were measured before and 4 h after intake of cetirizine or ebastine. RESULTS: Before treatment, concentration-response curves were similar and threshold concentrations identical (0.57 mg/ml and 0.57 mg/ml for cetirizine and ebastine, respectively). Both treatments exerted a significant effect. However, cetirizine was significantly more efficient than ebastine 20 mg (P < 0.01 both for wheals and flares). After cetirizine, the threshold concentration inducing a 3-mm(2 )wheal was significantly higher (266 mg/ml) than after ebastine (77 mg/ml) (P < 0.01), and total inhibition of the wheal was obtained in 18 of 24 patients for cetirizine and in 4 of 24 for ebastine (P < 0.001). The variation coefficient for the wheal reaction was 31% for cetirizine and 159% for ebastine, indicating a much lower variability after cetirizine. CONCLUSION: Our study shows clearly that the efficacy of a single therapeutic dosage of cetirizine is greater and consistently better than that of ebastine for suppression of cutaneous reactivity to histamine 4 h after treatment in healthy volunteers. The need for ebastine to metabolise into the active carebastine might explain this difference.

Consistency of the efficacy of cetirizine and ebastine on skin reactivity.

BACKGROUND: At therapeutic dosage, cetirizine and ebastine induce significant inhibition of skin reactivity to histamine. The consistency of their efficacy, that is, efficacy with the least interindividual variability among subjects, has not been carefully assessed, however. OBJECTIVE: To compare the consistency and efficacy of these antihistamines on skin reactivity. METHODS: Twenty-four healthy volunteers participated in a randomized double-blind crossover study. The areas of wheals and flares induced by increasing (0, 5, 10, 50, 100, 200, and 300 mg/mL) histamine concentrations, administered by prick tests, were measured before and four hours after intake of 10 mg of each antihistamine, allowing concentration-response curves to be established. The threshold histamine concentrations inducing wheal areas of 3 mm2 (positivity) were calculated by interpolation. The coefficient of variation (SD/mean %) was used to evaluate the consistency of the response. RESULTS: Pretreatment concentration-response curves were similar, and threshold concentrations identical (0.29 mg/mL and 0.34 mg/mL for cetirizine and ebastine, respectively). For both, curves were lower after treatment than before. After cetirizine, the threshold concentration was significantly higher (217 mg/mL) than after ebastine (0.82 mg/mL) (P < .001), and total inhibition of the wheal reaction was observed in 21 of 24 patients at the lowest histamine concentration and in 17 of 24 at the highest. Ebastine never totally inhibited reaction, even to 5 mg/mL of histamine. Over the entire concentration-response curve, the coefficient of variation for the wheal reaction was 6.3% for cetirizine and 72.6% for ebastine, and, for flares, 11.0% and 83.7%, respectively. Hence, variability was much lower after cetirizine. CONCLUSION: Our study shows clearly that the efficacy of a single therapeutic dosage of cetirizine is consistently good for suppression of cutaneous reactivity to histamine in healthy volunteers. The need for ebastine to metabolize into the active carebastine might explain its lesser consistency.

Nasal effect of cetirizine and loratadine at 24 hours in patients with allergic rhinitis.

Numerous studies have compared the duration of the cutaneous effect of cetirizine and loratadine. We assessed their nasal effects 24 hours after administration in patients with allergic rhinitis, using a randomized, double-blind, crossover, placebo-controlled trial. Nasal challenge was performed by nebulization of increasing doubling dosages of histamine (0.04-1.28 mg/nostril) in 12 patients (seven males, five females, aged 31 +/- 7 years). Nasal airway resistance was measured by posterior rhinomanometry 24 hours after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline nasal airway resistance was identical on all study days (2.86 +/- 0.10 cm H2 O/L per second). Twenty-four hours after intake, the dose-response curve of nasal obstruction to histamine was significantly lower after treatment with cetirizine compared with placebo (P < 0.05). However, although the curve was lower on loratadine than on placebo, the curves did not differ significantly. In conclusion, our study shows significant efficacy of cetirizine, but not of loratadine, in the nose at 24 hours after a single dose. This suggests that the nasal action of cetirizine is longer lasting than that of loratadine in patients with allergic rhinitis.

Onset of action in the nasal antihistaminic effect of cetirizine and loratadine in patients with allergic rhinitis.

Several studies have compared the cutaneous efficacy of cetirizine and loratadine and their onset of action. We assessed the nasal effect of these two antihistamines in a randomized, double-blind, crossover, placebo-controlled trial in order to compare objectively their efficacy and onset of action in the noses of patients with allergic rhinitis. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0, 0.04-1.28 mg/nostril) in 12 patients (eight men, four women, aged 22-39 years). Nasal airway resistance (NAR) was measured by posterior rhinomanometry either 1.5 h or 4 h after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline NAR was identical between all study days (2.60-2.88 cmH2O.l-1.s). One and a half hours after intake, the increase in NAR induced by histamine was significantly reduced by both cetirizine and loratadine in contrast to placebo. However, with cetirizine the nasal obstruction was significantly lower than with loratadine (P < 0.05). Four hours after intake, a similar inhibition of the nasal obstruction caused by histamine was observed with both cetirizine and loratadine (P < 0.05). In conclusion, this study found cetirizine and loratadine to have similar nasal efficacy at therapeutic dosage 4 h after intake, whereas cetirizine was more effective than loratadine 1.5 h after intake. In agreement with the results observed in the skin, our study suggests a more rapid onset of action of cetirizine in the nose in allergic rhinitis.