Bambuterol in the treatment of asthma. A placebo-controlled comparison of once-daily morning vs evening administration.
Once-daily morning (7 AM) vs evening (10 PM) administration of the terbutaline prodrug bambuterol (20-mg tablet dose) was investigated in a double-blind, cross-over, randomized, and placebo-controlled study involving 29 diurnally active patients with asthma. Terbutaline plasma concentration, spirometry, and drug tolerance were assessed during 39-h inpatient studies. A 7-day washout period separated each treatment. Mean 24-h plasma concentration was comparable for morning and evening bambuterol (13.2 vs 14.0 nmol/L). The Cmax for evening vs morning dosing was 17.2 vs 15.5 nmol/L (p < 0.02). The 24-h mean FEV1 was greater (p < 0.001) for bambuterol (morning: 3.2 L; evening: 3.4 L) vs placebo (2.9 L) as it was for FVC, FEF25-75%, and peak expiratory flow rate (PEFR), with the maximum effect at 4 AM independent of medication time. Evening dosing, however, resulted in greatest 7 AM (awakening) FEV1, FEV25-75, and PEFR (p < 0.03). With reference to corresponding-in-time placebo values, improvement in FEV1 at the end of the 24-h dosing intervals amounted to 0.34 L (13.5%) (p < 0.0004) and 0.35 L (15.9%) (p < 0.0012) with evening and morning bambuterol dosing, respectively. Side effects were greater for bambuterol than placebo, but not significantly so. Once-daily bambuterol therapy proved to be an effective treatment for asthma, whether administered in the evening or morning. Evening dosing seems best for nocturnal asthma since airway patency overnight and on awakening at 7 AM is most improved.
D'Alonzo
G E
GE
School of Medicine, University of Texas Health Science Center at Houston.
Smolensky
M H
MH
Feldman
S
S
Gnosspelius
Y
Y
Karlsson
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002802:Cholinesterases / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D013726:Terbutaline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D001993:Bronchodilator Agents; D002802:Cholinesterases; D013726:Terbutaline; C047766:bambuterol