Bronchodilator and bronchoprotective effects of cilostazol in humans in vivo.
Cilostazol is a selective orally active phosphodiesterase (PDE) III inhibitor. This study was conducted to evaluate whether inhibition of PDE subtype III can reduce bronchial responsiveness. We examined the effects of cilostazol on bronchial responsiveness to methacholine in eight normal subjects by a single-blinded, crossover study. Each subject received 200 mg of cilostazol or placebo in random order. The subjects underwent methacholine challenge test 3 h after administration of each drug on two occasions separated by 5 d or more. The geometric mean value of provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) and the mean value (+/- SEM) of maximum expiratory flow on partial flow-volume curve at isovolume of 40% FVC above residual volume (PEF40) after administration of cilostazol were 25.3 (geometric standard error of the mean [GSEM], 1.35) mg/ml and 3.78 +/- 0.31 L/s, which were significantly (p < 0.02 and p < 0.05) greater than those after the placebo administration (6.81 [GSEM, 1.42] mg/ml and 2.71 +/- 0.39 L/s). All subjects complained of mild to severe headache when cilostazol was given. These findings suggest that PDE III inhibitors such as cilostazol have bronchodilator and bronchoprotective effects in humans. Further studies regarding smaller oral dosing of or aerosol administration of cilostazol or the other PDE III inhibitors are needed to determine clinical usefulness.
Fujimura
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa University Hospital, Japan.
Kamio
Y
Y
Saito
M
M
Hashimoto
T
T
Matsuda
T
T
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000328:Adult; D001985:Bronchial Provocation Tests / Q000379:methods / Q000706:statistics & numerical data; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D000077407:Cilostazol; D018592:Cross-Over Studies; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016210:Methacholine Chloride; D012016:Reference Values; D016037:Single-Blind Method; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
D001993:Bronchodilator Agents; D013777:Tetrazoles; D016210:Methacholine Chloride; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol