A comparative study in atopic subjects with asthma of the effects of salmeterol and salbutamol on allergen-induced bronchoconstriction, increase in airway reactivity, and increase in urinary leukotriene E4 excretion.
Salmeterol (SM) is a novel beta 2-adrenoceptor agonist with a duration of action in excess of 12 hours. Evidence from in vitro studies has also demonstrated that, unlike the short-acting beta 2-agonists, such as salbutamol (SB), it may have some anti-inflammatory properties. With a randomized, double-blind, crossover design, we have compared the inhibitory effects of SM (50 micrograms) and SB (200 micrograms) delivered by metered-dose inhaler on allergen-induced bronchoconstriction, changes in airway reactivity, and urinary leukotriene (LT) E4 excretion in 12 atopic subjects with mild asthma. The immediate bronchoconstriction to allergen was significantly reduced by both beta 2-agonists (p less than 0.005), when reduction was expressed either in terms of maximum fall in FEV1 at 15 minutes after allergen (percent fall in FEV1, mean +/- SEM: 6.2 +/- 4.9, SM; 5.7 +/- 2.5, SB; 40.4 +/- 6.3, placebo) or the area under the FEV1 time curve (AUC) for the first 120 minutes after allergen. Four hours after challenge, results in the SB-treated and placebo-treated groups were not significantly different and demonstrated a small persistent bronchoconstriction compared to bronchodilatation in the SM-treated group (percent fall in FEV1, respectively, 9.3 +/- 3.7, 14.3 +/- 7.1, and -6.3 +/- 2.7; p less than 0.005, SM versus SB; p less than 0.02, SM versus placebo). Expressed in terms of AUC, only SM significantly reduced bronchoconstriction in the period 120 to 240 minutes after allergen (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, England.
I K
IK
Taylor
K M
KM
O'Shaughnessy
N B
NB
Choudry
M
M
Adachi
J B
JB
Palmer
R W
RW
Fuller
D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000485:Allergens; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D001985:Bronchial Provocation Tests / Q000379:methods; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D017999:Leukotriene E4; D013189:SRS-A / Q000031:analogs & derivatives* / Q000652:urine; D000068299:Salmeterol Xinafoate; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000485:Allergens; D013189:SRS-A; D000068299:Salmeterol Xinafoate; D017999:Leukotriene E4; D000420:Albuterol