A double-blind, placebo-controlled trial of the thromboxane synthetase blocker OKY-046 on bronchial hypersensitivity in bronchial asthma patients.
We investigated the effect of thromboxane (TX) synthetase inhibitor, OKY-046, on bronchial hypersensitivity in 16 asthmatics by a double-blind, placebo-controlled, crossover trial. Bronchial sensitivity to methacholine was measured by Astograph. Blood samples were taken to measure plasma levels of TX metabolites. No significant differences of forced expiratory volume in 1 sec (FEV1), bronchial sensitivity, or bronchial reactivity were observed after OKY-046 administration, compared to baseline or after placebo. However, responders showed a significant decrease in the plasma TXB2/6-keto-PGF1alpha ratio as compared to nonresponders. Our data failed to confirm an inhibitory effect of OKY-046 on bronchial hypersensitivity, but suggested the importance of its therapeutic dose monitoring.
Kunitoh
H
H
Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, Japan. hkkunito@gan2.ncc.go.jp
Watanabe
K
K
Nagatomo
A
A
Okamoto
H
H
Nakagawa
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D013147:Spirometry; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D008689:Methacrylates; D010919:Placebos; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase; C034364:ozagrel