Assessment of bronchial effects following topical administration of butylamino-phenoxy-propanol-acetate, an oculoselective beta-adrenoceptor blocker in asthmatic subjects.
1. Butylamino-phenoxy-propanol-acetate (BPPA) is a new topical oculoselective beta-adrenoceptor blocker for the reduction of intraocular pressure (IOP) in man. Its potency on the airways of normal subjects was identical with that of placebo. A study was carried out to determine the potential of BPPA to cause bronchoconstriction in mild asthmatics (FEV1 greater than or equal to 60% predicted) with normal IOP. 2. Twelve nonsmoking outpatients who bronchoconstricted to 0.25 or 0.50% of timolol eye drops (fall in FEV1 23.33 +/- 1.20% (mean +/- s.e. mean), range 16-30) were investigated in this double-masked, randomized, 3-period, crossover study. On three different occasions six incremental concentrations of BPPA (range: 0.1-2%; maximum cumulative concentration 4%), timolol (0.1-1%; 2%), and placebo were administered bilaterally until bronchoconstriction (decrease in FEV1 greater than or equal to 20% and in specific airway conductance (sGaw) greater than or equal to 35% simultaneously) or the maximum cumulative concentration was reached. 3. Airway response was measured as change in FEV1 and sGaw and dose-response curves to timolol, BPPA and placebo were performed. IOP was measured 3 h after the highest concentration of each study day. 4. Timolol caused dose-dependent falls in FEV1 and sGaw as well as clinical symptoms of respiratory distress in all subjects. The median cumulative concentrations of timolol required to decrease FEV1 by 20% and sGaw by 35% were 0.98% and 1.53%. Neither placebo (P greater than 0.05) nor BPPA (P greater than 0.05) caused a significant change in sGaw. A fall in FEV1 by 20% not accompanied by a simultaneous fall in sGaw by 35% was found in four subjects following BPPA and in five subjects following placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
Bauer
K G
KG
Division of Internal Medicine I, University of Vienna Medical School, Austria.
Brunner-Ferber
F
F
Distlerath
L M
LM
Lippa
E A
EA
Binkowitz
B
B
Till
P
P
Kaik
G A
GA
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D005541:Forced Expiratory Volume / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011412:Propanolamines / Q000008:administration & dosage / Q000009:adverse effects*; D011480:Protease Inhibitors / Q000494:pharmacology*; D015656:Respiratory Mechanics / Q000187:drug effects; D013999:Timolol / Q000009:adverse effects / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D011412:Propanolamines; D011480:Protease Inhibitors; C055890:L 653328; D013999:Timolol