Effect of cysteinyl-leukotriene receptor antagonist ICI 204.219 on allergen-induced bronchoconstriction and airway hyperreactivity in atopic subjects.
The effects of a highly selective leukotriene D4 receptor antagonist, ICI 204.219, on allergen-induced bronchoconstriction and changes in airway reactivity were evaluated in a double-blind, placebo-controlled, crossover trial. Ten atopic subjects were selected for the study on the basis of an immediate fall in forced expiratory volume in 1 s (FEV1) of at least 15% and a least a doubling dose fall in their PC20-histamine (the concentration of histamine needed to reduce FEV1 by 20%) after antigen challenge. Baseline PC20-histamine was determined before the ingestion of a single oral 40 mg dose of ICI 204.219 or matched placebo. 2 h later subjects were challenged with aerosolised allergen; FEV1 was measured for the next 6 h then PC20-histamine was remeasured. Two subjects did not complete the study for reasons not related to the trial medication. ICI 204.219 significantly attenuated the early and late phase bronchoconstriction to inhaled allergen (mean treatment difference in area under the FEV1-time curves 2529 [95% Cl 1085-3972] delta %FEV1.min; p less than 0.005: and 3537 [528-6545] delta %FEV1.min; p less than 0.03) and suppressed the allergen-induced increase in non-specific bronchial reactivity (mean treatment difference 1.03 [0.34-1.71] doubling dilutions of histamine; p less than 0.01). These findings suggest that ICI 204.219 may be a disease-modifying agent in asthma. Further studies are under way to evaluate its clinical efficacy.
Taylor
I K
IK
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, UK.
O'Shaughnessy
K M
KM
Fuller
R W
RW
Dollery
C T
CT
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage / Q000494:pharmacology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007211:Indoles; D015289:Leukotrienes; D008297:Male; D048448:Phenylcarbamates; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D012882:Skin Tests; D013449:Sulfonamides; D013997:Time Factors; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D000336:Aerosols; D000485:Allergens; D007211:Indoles; D015289:Leukotrienes; D048448:Phenylcarbamates; D011971:Receptors, Immunologic; D013449:Sulfonamides; D014105:Tosyl Compounds; D006632:Histamine; C027556:histamine phosphate; C062735:zafirlukast