The effect of the oral leukotriene antagonist, ICI 204,219, on leukotriene D4 and histamine-induced cutaneous vascular reactions in man.

Abstract Eighteen normal male subjects were recruited for a double-blind, placebo-controlled, randomized, two-period crossover study to determine the effects of a new, potent, highly selective, oral peptide leukotriene antagonist (ICI 204,219) on cutaneous vasculture. Skin testing for leukotriene D 4 (LTD 4 ) and histamine was performed at three different time intervals after receiving ICI 204,219 or placebo. The LTD 4 threshold dose responses were recorded in duplicate to verify reproducibility. These data confirm known remarkable dose-response variation of cutaneous vascular reactions to LTD 4 since some subjects reacted to a dose as low as 0.001 fmol. Twelve subjects (67%) demonstrated a more than one-half log increase in their threshold response after receiving ICI 204,219. Five of these 12 subjects (28%) had >1 log-dose response after ICI 204,219. Two of these subjects (11.1%) had a 5 or 10 log increase in their threshold response after receiving ICI 204,219. Given the role of leukotrienes as potentially important mediators in immediate-type reactions, our results raise the possibility for additional investigation of the antagonistic effect of ICI 204,219 in nonallergic and allergic cutaneous diseases.