PHARMACODYNAMIC DOSE-FINDING OF DIMETINDENE IN A SUSTAINED-RELEASE FORMULATION

A sustained release form of dimetindene (dimethindene maleate, Fenisti l(R), CAS 3614-69-5) was developed based on a micropellet technique- A im of the study was to evaluate the efficacy and duration of two doses of dimetindene in a sustained release pellet formulation with a stand ardised grass pollen provocation model ( Vienna Challenge Chamber VCC) . The study with 12 grass pollen allergic volunteers - verified by cas e history, skin prick test (SPT), and radio allergo sorbent test (RAST ) - was carried out in a placebo controlled, double blind, cross-over design. 12 h before a 4-h-lasting continuous challenge with permanent 1000 dactylis grass pollen in the VCC, administration of dimetindene ( Fenistil R Pellets) in doses of 4 mg, 8 mg or identically appearing pl acebo was scheduled in three sessions Nasal flow and resistance, nasal secretion and subjective symptoms were recorded at 15-min intervals d uring this long-term challenge under reproducible conditions. In compa rison to placebo, dimetindene leads to a statistically significant red uction (p < 0.05) of nasal response and clinical symptoms for at least 16 h-after treatment. The efficacy of 8 mg dimetindene was pronounced over 4 mg, however, the differences between both active treatments we re not statistically significant. Therefore 4 mg dimetindene once a da y is the adequate treatment for usual pollinotic disease conditions.