Effects of aerosol administration of a thromboxane synthetase inhibitor (OKY-046) on bronchial responsiveness to acetylcholine in asthmatic subjects

Chest. 1990 Aug;98(2):276-9. doi: 10.1378/chest.98.2.276.

Abstract

Bronchial hyperresponsiveness is one of the major clinical features of bronchial asthma. We previously reported that oral administration of a selective thromboxane synthetase inhibitor, OKY-046, reduced bronchial hyperresponsiveness to acetylcholine in asthmatic subjects. In this study, the effect of aerosol administration of OKY-046 on bronchial hyperresponsiveness was evaluated in ten inpatients with intrinsic asthma. Acetylcholine inhalation tests were performed before and after four days of inhalation of OKY-046 (100 mg/day). The provocative concentration of acetylcholine producing a 20 percent fall in forced expiratory volume in 1 s (PC20-FEV1) and that causing a 35 percent fall in respiratory conductance (PC35-Grs) were measured as indexes of bronchial responsiveness. There was a significant increase in PC20-FEV1 (p less than 0.001) and PC35-Grs (p less than 0.02) after inhalation of OKY-046 from 0.79 (GSEM, 1.41) Mg/ml and 0.96 (GSEM, 1.35) mg/ml to 1.20 (GSEM, 1.41) mg/ml and 1.74 (GSEM, 1.32) mg/ml, respectively. There was no significant difference in forced vital capacity (FVC), FEV1, or respiratory resistance (Rrs) baseline values before and after inhalation of OKY-046. Platelet aggregation was not inhibited by the treatment in other five inpatients. Thus, prophylactic administration of aerosol OKY-046 may be available for treatment of asthma by reduction of bronchial hyperresponsiveness. Further studies are needed to determine the optimum dose.

MeSH terms

  • Acetylcholine*
  • Acrylates / therapeutic use*
  • Administration, Inhalation
  • Aerosols
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Bronchial Provocation Tests
  • Bronchial Spasm / chemically induced
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Methacrylates / administration & dosage
  • Methacrylates / therapeutic use*
  • Middle Aged
  • Thromboxane-A Synthase / antagonists & inhibitors*

Substances

  • Acrylates
  • Aerosols
  • Methacrylates
  • Thromboxane-A Synthase
  • ozagrel
  • Acetylcholine