Medicine of the Future in America

Inhaled ICI 204,219 Blocks Antigen-Induced Bronchoconstriction in Subjects With Bronchial Asthma: Discussion

Twenty-seven adverse events were recorded for ten subjects. All adverse events were mild (n = 16) or moderate (n = 11); the most common events were headache (n = 6), rhinitis (n = 4), and cough (n = 3). No serious or unexpected adverse events were attributed to ICI 204,219.
Clinical laboratory tests showed a significant (p = 0.02) treatment difference in white blood cell count, with subjects taking formulation 1 having a significantly lower count than subjects taking formulation 2 (p = 0.006, 5.71 vs 6.35 x 103/L). This difference was not deemed to be clinically significant. Findings from physical examinations, electrocardiograms, and vital signs measurements were not statistically significantly different from baseline after treatment with ICI 204,219.
Our results indicate that inhalation formulations of ICI 204,219 successfully inhibited bronchoconstriction in subjects with reproducible sensitivity to ragweed challenges. Inhaled ICI 204,219, given 30 min before ragweed challenge, produced total inhibition of ragweed-induced bronchoconstriction in 31 of 39 challenges in 13 subjects with mild asthma who were tested in the absence of environmental exposure to ragweed. There were no differences in the results of antigen bronchoprovocation when patients were tested either 3 days or 4 weeks apart. Antigen-induced bronchoprovocation, therefore, appears to be a useful model to evaluate the efficacy of leukotriene receptor antagonists for the treatment of asthma, provided appropriate steps are taken to ensure the accuracy of the bronchoprovocation test results. In this study, in contrast to a previous study, we required subjects to have two reproducible screening provocations with ragweed before they underwent bronchoprovocation. canadian neightbor pharmacy

ICI 204,219 did not act as a bronchodilator. In preclinical studies, ICI 204,219 was shown to be a potent antagonist of LTD4 receptors, but it had no effect on other receptors. ICI 204,219, administered as a single 40-mg oral dose, was shown to be a potent antagonist of LTD4-induced bronchoconstriction in normal subjects. In our study, inhibition of ragweed-induced bronchoconstriction after administration of ICI 204,219 occurred in the absence of any improvement in FEV,. In addition, changes in plasma concentrations of ICI 204,219 had no effect on blocking ragweed-induced bronchoprovocation, as varying drug plasma concentrations were observed at 30 min and 2 h after dosing for each formulation of drug.
This study was performed in an open-label fashion to compare the three formulations. Either two separate studies or a six-way crossover design would have been necessary to maintain a double-blind study during a limited time period (zero ambient ragweed counts).

This entry was posted in Asthma and tagged asthma, bronchoconstriction, bronchoprovocation test, leukotriene.
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