The leukotriene D4-receptor antagonist, ICI 204,219, relieves symptoms of acute seasonal allergic rhinitis.

Abstract

The efficacy and safety of single oral doses of the leukotriene D4-receptor antagonist, ICI 204,219, were tested in subjects with acute seasonal allergic rhinitis. Subjects who were enrolled in the double-blind, placebo-controlled trial spent 8 h/d for two consecutive days in a park at the peak of ragweed season (counts > 1,000 grains/m3). Subjects (n = 164) who had sufficient symptoms during a 3-h baseline period on Day 1 were randomized to treatment with 10 (n = 33), 20 (n = 33), 40 (n = 33), or 100 mg (n = 32) of ICI 204,219 or placebo (n = 33). Rhinitis symptoms (nasal congestion, sneezing, rhinorrhea, itchy nose, throat and palate, and eye symptoms) were recorded hourly in the park and three times each evening at home. Blood samples were collected twice daily to determine plasma levels of ICI 204,219. Nasal congestion improved (p < 0.01) most consistently from the evening of Day 1 through Day 2 after treatment with 20- and 40-mg doses of ICI 204,219 versus placebo. Sneezing and rhinorrhea (p < or = 0.05) also improved on Day 2 for subjects who received 20- and 40-mg doses of ICI 204,219 compared with placebo. Mean symptoms scores for the entire day showed that 20 mg of ICI 204,219 was the minimally effective dose in this trial. The onset of action for all treatment groups, including placebo, was within the first 2 h of dosing. No serious adverse events were reported during the trial. ICI 204,219 was well tolerated and relieved symptoms of acute seasonal allergic rhinitis.

Acquired Nasal Hyperresponsiveness Aggravates Antigen-Induced Rhinitis in the Guinea Pig

“…These reported findings almost completely agree with the present effectiveness of the drugs after the disappearance of hyperresponsiveness, suggesting that the influence of nasal hyperresponsiveness to stimuli on antigen-induced nasal symptoms may be substantially excluded in the other models. On the other hand, a double-blind, placebocontrolled trial of a CysLT antagonist, zafirlukast, in patients with acute seasonal (ragweed) allergic rhinitis revealed that the drug significantly suppressed not only nasal congestion but also sneezing (5). Based on this finding, CysLTs are involved in the induction of sneeze in the clinical setting.…”

“…Because sneezing and watery rhinorrhea in allergic rhinitis could be inhibited by treating patients with antihistaminics, these symptoms are triggered mainly via the stimulation of nasal terminals of the trigeminus nerve by histamine (4). Although the detailed sequence of events leading to the occurrence of allergic nasal blockage are not yet fully elucidated, it has been reported that a cysteinyl leukotriene (CysLT)-receptor antagonist reduced nasal blockage (5,6).…”

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008*

“…Park studies have been used to assess the onset and magnitude of efficacy of treatments for pollen-induced allergic rhinitis (1324,1325).…”

Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs

“…The oral route of administration appears to carry some possible advantages over conventional therapies. Apart from the potentially favourable effect of oral admininistration on patient compliance with asthma therapy, there are several indications that antileukotrienes also prevent some of the symptoms in rhinitis (254)(255)(256). It is well established that a large proportion of asthmatics suffer from rhinitis [257] and it would therefore seem to be an added benefit for this new group of asthma medication to alleviate some of the rhinitic symptoms as well.…”