Effect‐kinetic characterization of dimethindene maleate following oral administration (Fenistil, Tropfen)

Abstract

Dimethindene maleate is a well known H1-receptor antagonist with strong affinity to the H1-receptor. In order to evaluate the time course of its activity, dimethindene maleate was investigated in a histamine provocation model in man. Eight healthy male volunteers were treated either with 4 mg dimethindene maleate using a commercially available solution (Fenistile, Tropfen) or an identically appearing placebo solution (po) following a double-blind, crossover study design. Intracutaneous histamine injections were administered at -1, 2, 5, 14, 17, 20, 23, 26 and 29 h following drug administration. Areas of flares and weals were measured 5, 10, 20, and 30 min following histamine provocation. A strong inhibition of the development of flares and weals was observed to be more pronounced in flares than in weals. Baseline adjusted areas under the curve differ statistically significantly following verum and placebo treatment conditions (P = 0.0028). According to the time schedule of the study maximal effects were observed at time point 5 h. The mean residence times of the inhibitory effects were calculated to be congruent to 13 h compared to the mean residence times of dimethindene blood levels of approximately 8 h indicating a non-linear relationship between blood level and effect.