Bronchodilator effects of intravenous olprinone, a phosphodiesterase 3 inhibitor, with and without aminophylline in asthmatic patients.
OBJECTIVE
There is no evidence demonstrating the clinical usefulness of phosphodiesterase (PDE) inhibitors in the treatment of asthma, although PDE3 and 4 inhibitors have received much attention for the treatment of bronchial asthma. We compared the bronchodilator effects of intravenously administered olprinone, a selective PDE3 inhibitor, and aminophylline, a nonselective PDE inhibitor, both alone and concomitantly.


METHODS
In 12 patients with mild stable asthma, we compared the acute bronchodilator effects of the following two drugs, alone and together using a double-blind crossover design: intravenous administration of olprinone, 30 micro g min-1; aminophylline, 2.25 mg min-1; and olprinone plus aminophylline over a total period of 150 min.


RESULTS
Mean maximal increase (95% confidence interval) in the FEV1 was 7.8% (2.4, 13.2), 17.1% (10.0, 24.2), 16.6% (11.2, 22.0), and 1.0% (-1.1, 3.1) during infusion of aminophylline, olprinone, aminophylline and olprinone, and saline, respectively. The magnitude of bronchodilatation produced by olprinone was greater than that by aminophylline. The combination of aminophylline and olprinone did not produce any greater bronchodilatation than olprinone alone. Olprinone alone or in combination with aminophylline lowered diastolic blood pressure, and increased heart rate.


CONCLUSIONS
These results suggest that the intravenous administration of PDE3 inhibitors exhibits a bronchodilatory effect. There are no additive or synergistic effects of administration of olprinone and aminophylline at the same time.
Myou
Shigeharu
S
Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan. myous@nifty.com
Fujimura
Masaki
M
Kamio
Yumie
Y
Hirose
Tatsuki
T
Kita
Toshiyuki
T
Tachibana
Hideki
H
Ishiura
Yoshihisa
Y
Watanabe
Kazuyoshi
K
Hashimoto
Takuma
T
Nakao
Shinji
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000328:Adult; D000628:Aminophylline / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011728:Pyridones / Q000008:administration & dosage*; D014797:Vital Capacity / Q000187:drug effects
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D000628:Aminophylline; C059498:olprinone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3