Pharmacodynamic dose finding of dimetindene in a sustained release formulation

A sustained release form of dimetindene (dimethindene maleate, Fenistil, CAS 3614-69-5) was developed based on a micropellet technique. Aim of the study was to evaluate the efficacy and duration of two doses of dimetindene in a sustained release pellet formulation with a standardised grass pollen provacation model (Vienna Challenge Chamber; VCC). The study with 12 grass pollen allergic volunteers--verified by case 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 placebo was scheduled in three sessions. Nasal flow and resistance, nasal secretion and subjective symptoms were recorded at 15-min intervals during this long-term challenge under reproducible conditions. In comparison to placebo, dimetindene leads to a statistically significant reduction (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 were not statistically significant. Therefore 4 mg dimetindene once a day is the adequate treatment for usual pollinotic disease conditions.