Effect time-course of the inhibition of histamine induced skin reactions by orally applied dimethindene maleate

We have investigated the time-course of the 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 orally applied, followed by intracutaneous histamine provocations (−1, 2, 5, 14, 17, 20, 23, 26, 29 h). The two cross-over periods were separated by a wash-out phase of 17 h. Flare areas were documented 5, 10, 20 and 30 min after provocation with histamine. A strong inhibition of the development of flares was observed. With regard to the time-course of the inhibiting effect, its maximum was observed at a provocation time of 5 h. The mean residence time of the inhibiting effect was calculated to be ca. 13 h. This is different from the mean residence time of ca. 8 h obtained from blood level data. Blood- and effect-levels are not linearly related under oral treatment conditions.