[Comparative activity of antihistamines on area under dose-response curve from histamine-induced wheal and flare responses in human skin]

Abstract

Objective: To compare the activity of antihistamines by the index of area under dose-response curve (AUDRC) obtained from histamine-induced wheal and flare reactions.

Methods: Mizolastine 10 mg, loratadine 10 mg, and placebo were given to 90 healthy volunteers and 60 allergic patients in a double-blind and randomized manner. Histamine titration tests (histamine concentrations 54.3, 20.0, 7.3, and 2.7 mmol/L) were performed for each one before dosing and 2, 4, and 24 hours after dosing. The reactivity was evaluated by histamine-induced wheal and flare areas. The AUDRC values of the wheal and flare areas as a function of the natural logarithm transformed histamine concentration were calculated for each subject, and compared.

Results: There was no significant difference of the wheal and flare areas between health volunteers and allergic patients. The AUDRC(27-54.3 mmol/l.) for wheal and flare of mizolastine was 115.7, 23.4, 7.7, 49.8 and 902.1, 40.9, 2.6, 46.9 ln (mmol/L) x mm2 at each time (before dosing and 2, 4, 24 hours after dosing) respectively. Compared with loratadine [116.2, 80.2, 49.7, 71.9 and 957.6, 495.3, 153.5, 205.9 ln (mmol/L) x mm2], mizolastine decreased AUDRC(2.7 - 54.3 mmol/L significantly (P < 0.01).

Conclusion: Histamine-induced wheal and flare inhibition test is a reliable pharmacodynamic model for antihistamines, and AUDRC may be an useful index to predict antihistamines pharmacodynamic activity.