The Leukotriene Receptor Antagonist Zafirlukast Inhibits Sulfur Dioxide–induced Bronchoconstriction in Patients with Asthma
| Autor: | Michael J. Watts, Stephen C. Lazarus, Hofer Wong, Margaret C. Minkwitz, Bernard J. Lavins, Homer A. Boushey |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine medicine.medical_specialty Indoles Bronchoconstriction Phenylcarbamates Critical Care and Intensive Care Medicine complex mixtures Tosyl Compounds Double-Blind Method Forced Expiratory Volume Internal medicine Hyperventilation medicine Humans Sulfur Dioxide Anti-Asthmatic Agents Zafirlukast Asthma Sulfonamides Cross-Over Studies Dose-Response Relationship Drug Inhalation Leukotriene receptor business.industry Airway Resistance medicine.disease Crossover study respiratory tract diseases Endocrinology Bronchial hyperresponsiveness Leukotriene Antagonists Female medicine.symptom business medicine.drug |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 156:1725-1730 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/ajrccm.156.6.9608006 |
| Popis: | Inhalation of sulfur dioxide (SO2) causes bronchoconstriction in most people with asthma. To examine the role of leukotrienes in this response, the antagonism of SO2-induced bronchoconstriction by a single oral dose of the leukotriene receptor antagonist zafirlukast was assessed in a double-blind, placebo-controlled, two-period crossover trial in 12 subjects with mild-to-moderate asthma. Subjects had bronchial hyperresponsiveness, an FEV1or = 70% of predicted, and a positive response to inhaled SO2 (an 8-unit increase in specific airway resistance on inhaling an SO2 concentration ofor = 4 ppm (PC8SRaw). Subjects were treated with zafirlukast (20 mg) or placebo on two treatment days 5 to 14 d apart. Two and 10 hours after treatment, subjects inhaled SO2 (0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 ppm) during eucapnic hyperventilation at 20 L/min. PC8SRaw was determined after each challenge. Blood samples were collected to assess zafirlukast plasma concentrations versus effect. PC8SRaw was significantly higher 2 h after zafirlukast compared with placebo (3.1 versus 1.5 ppm; p = 0.02) and remained higher 10 h after treatment with zafirlukast (2.7 versus 1.9 ppm; p = 0.09). An association was found between zafirlukast plasma concentrations and increases in PC8SRaw 10 h after treatment (p = 0.001). The safety profile of zafirlukast was not clinically different from placebo. A single 20-mg dose of zafirlukast attenuated SO2-induced bronchoconstriction. We conclude that S02-induced bronchoconstriction involves release of leukotrienes and that treatment with zafirlukast attenuates the bronchoconstrictor response. |
| Databáze: | OpenAIRE |
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