Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma.
The airway and tremor response and cardiovascular and hypokalemic effects of single doses of inhalative fenoterol dry powder capsules (0.4 mg) were compared with the fenoterol metered dose inhaler (0.4 mg) and colforsin (forskolin) dry powder capsules (10.0 mg), a direct activator of the adenylate cyclase system, in 16 patients with asthma. Subjects (FEV1 < or = 60% predicted) were investigated in a randomized, double-masked, placebo-controlled, four-period, crossover trial for a 120 minute period. All active drugs caused a significant increase in specific airway conductance (p < 0.05); the order of potency (mean +/- SEM maximum increase from baseline) was fenoterol metered dose inhaler (0.51 +/- 0.06 sec-1 x kPa-1), fenoterol dry powder capsules (0.49 +/- 0.07), and colforsin dry powder capsules (0.30 +/- 0.03). A marked increase in finger tremor amplitude resulted after fenoterol metered dose inhaler only (62.93% +/- 10.21%; p < 0.05) in contrast to fenoterol dry powder capsules (15.84% +/- 4.35%; p < 0.05) and colforsin dry powder capsules (12.87% +/- 10.44%; p > 0.05). A decrease in plasma potassium was found after fenoterol (metered dose inhaler > dry powder capsules; p < 0.05). In conclusion, fenoterol dry powder capsules caused less tremor response and hypokalemic effects than the metered dose inhaler, although the bronchodilator capacity was similar. Colforsin dry powder capsules resulted in a measurable bronchodilatation in patients with asthma.
Bauer
K
K
Department of Internal Medicine, University of Vienna Medical School, Austria.
Dietersdorfer
F
F
Sertl
K
K
Kaik
B
B
Kaik
G
G
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects; D002214:Capsules; D005576:Colforsin / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005280:Fenoterol / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008448:Maximal Expiratory Flow Rate / Q000187:drug effects; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D011208:Powders; D011897:Random Allocation
D002214:Capsules; D011208:Powders; D005576:Colforsin; D005280:Fenoterol; D011188:Potassium