title: Effects of aerosol administration of a thromboxane synthetase inhibitor (OKY-046) on bronchial responsiveness to acetylcholine in asthmatic subjects.
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.
authors.affiliation: Third Department of Internal Medicine, Kanazawa, University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fujimura
authors.forename: S
authors.initials: S
authors.lastname: Nishioka
authors.forename: I
authors.initials: I
authors.lastname: Kumabashiri
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: J
authors.initials: J
authors.lastname: Mifune
mesh_terms: D000109:Acetylcholine; D000179:Acrylates / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000336:Aerosols; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000139:chemically induced; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
chemical_list: D000179:Acrylates; D000336:Aerosols; D008689:Methacrylates; D013930:Thromboxane-A Synthase; C034364:ozagrel; D000109:Acetylcholine