COMPARISON OF A NEW ANTIHISTAMINIC AND ANTIALLERGIC COMPOUND KW-4679 WITH TERFENADINE AND PLACEBO ON SKIN AND NASAL PROVOCATION IN ATOPIC INDIVIDUALS

The effects of three oral doses of a new compound KW 4679 thought to h ave both antihistaminic and antiallergic properties were compared with terfenadine and placebo in a double-blind cross-over trial in 15 volu nteers with seasonal allergic rhinitis. Comparison of the effect of th e treatments with either 2.5, 5 or 10 mg b.i.d. of KW 4679, 60 mg b.i. d. of terfenadine or placebo was made on the response to histamine and grass pollen skin-prick testing. Nasal provocation testing with grass pollen was performed on the eighth day of treatment. Nasal airway res istance (NAR) was measured using active posterior rhinomanometry and t he dose of grass pollen which caused a 200% increase in NAR was determ ined. The number of sneezes in the first 12 min was counted. Compared with placebo all doses of KW 4679 and terfenadine significantly inhibi ted the skin weal response to histamine and grass pollen (P < 0.001). The inhibitory effect of KW 4679 on both histamine and allergen induce d skin weals was significantly greater than that of terfenadine (P = 0 .001 and P = 0.049 respectively). The results of nasal challenges with grass pollen showed that all doses of KW 4679 and terfenadine were ef fective in reducing sneeze counts (P < 0.001), though there were no si gnificant effects on allergen induced increase in NAR. All three doses of KW 4679 were generally well tolerated. Drowsiness was reported by some of the volunteers on KW 4679 and one volunteer reported drowsines s whilst taking placebo. Slight and reversible rises in AST and ALT co ncentrations were observed; these were not considered clinically signi ficant.