Medicine of the Future in America

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

Inhaled ICI 204,219 Blocks Antigen-Induced Bronchoconstriction in Subjects With Bronchial Asthma: Efficacy AssessmentThe efficacy of ICI 204,219 was assessed by measuring pulmonary function before and after bronchoprovocation during each treatment period. Following administration of ICI 204,219, subjects inhaled five breaths of control aerosol consisting of saline solution solvent. Baseline FEV, and forced vital capacity (FVC) were measured 10 min later. A dose-response curve was then derived for each subject after administering five inhalations of antigen at each of a series of increasing concentrations, with 10- to 15-min intervals between successive concentrations. sildenafil citrate pink

The allergen concentrations used in provocations are presented in Table 1. The initial allergen dose for each subject (for periods 1, 2, and 3) was selected on the basis of results from the screening bronchial challenges. The starting concentration selected was one dilution number higher than the lowest concentration needed to provoke a decrease of 20 percent in FEV, (PC20) during the two screening challenges. Up to 8 doses of antigen were inhaled by each subject during the screening challenges, and up to 12 doses were administered on treatment days. The concentration of successive doses of antigen was doubled repeatedly until the FEV, decreased by at least 20 percent of the value obtained after the administration of the control aerosol, the maximum antigen concentration had been administered (100 iig/ml), or the subject had symptoms that warranted terminating the test. The same sequence of increases in antigen doses was repeated with each ragweed challenge performed on a particular subject. The FEV, and FVC were measured at 10-min intervals following each provocation dose until bronchoconstriction resolved.
In addition, blood samples were collected 30 min after administration of ICI 204,219 and at the conclusion of antigen-challenge testing (about 2 h after drug administration). Plasma levels of ICI 204,219 were detected by a high-performance liquid chromatography method with a fluorescence detector that had detection limit of 0.75 ng/ml (Drug Disposition and Metabolism Department, ZENECA Pharmaceuticals Croup, ZENECA Inc, Wilmington, Del).
Safety was determined from physical examination findings, measurements of vital signs, determinations of subjective symptoms, results of routine clinical laboratory tests, electrocardiographic findings, and spirometry.

Table 1—Allergen Concentrations During Bronchoprovocation Testing

ProvocationNo. DilutionNo. Ragweed Concentration, Mg/ml
1 12 0.05
2 11 0.1
3 10 0.2
4 9 0.39
5 8 0.78
6 7 1.56
7 6 3.13
8 5 6.25
9 4 12.5
10 3 25.0
11 2 50.0
12 1 100.0
This entry was posted in Asthma and tagged asthma, bronchoconstriction, bronchoprovocation test, leukotriene.
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