Effect-time-relation of the H1-receptor antagonist dimethindene maleate following intravenous injection.

We have investigated the time-course of the weal and flare inhibiting activity of dimethindene maleate in man and compared the resulting effect-kinetic data with those from pharmacokinetic investigations. The study was carried out in a double blind, placebo controlled cross-over design with randomly assigned healthy volunteers. Dimethindene maleate (4 mg) was intravenously injected, followed by intracutaneous histamine provocations (-1, 2, 5, 14, 17, 20, 23, 26, and 29 h). The two cross-over periods were separated by a wash-out phase of 17 h. Flare and weal areas were documented 5, 10, 20, and 30 min after provocation with histamine. A strong inhibition of the development of flares and weals was observed and was more pronounced in flares than in weals. With regard to the time course of the inhibiting effect, its maxima both for flares and weals were observed at a provocation time of 2 h. The mean residence time of the inhibiting effect was calculated to be ca. 13 h for flares and ca. 15 h for weals. These values are nearly 2-3 times as high as the mean residence time of 6 h calculated from blood level data. Blood- and effect-levels are thus non-linearly related.