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

METHODSMizolastine 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.

RESULTSThere 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).

CONCLUSIONHistamine-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.