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.
Horak
F
F
HNO-Universitätsklinik, Vienna, Austria.
Jäger
S
S
Nirnberger
G
G
Berger
U
U
Andresen
L
L
Vix
J M
JM
Rehn
D
D
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D003692:Delayed-Action Preparations; D004115:Dimethindene / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D015508:Nasal Obstruction / Q000503:physiopathology; D011058:Pollen / Q000276:immunology; D011852:Radioallergosorbent Test; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy; D012882:Skin Tests
D003692:Delayed-Action Preparations; D004115:Dimethindene