Abstract
The clinical pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of the long-acting beta 2-agonist salmeterol are reviewed. A MEDLINE search was performed to identify English-language publications pertaining to salmeterol. Open and controlled trials were reviewed in assessing clinical efficacy. Only the results of controlled, randomized trials were considered in the effectiveness evaluation. The primary measures of effectiveness in the clinical trials were bronchodilator activity and reduction of hyperresponsiveness that may reflect antiinflammatory activity. Bronchodilator activity was measured as changes in pulmonary function; reduction of hyperresponsiveness was evaluated using respiratory challenge with methacholine, histamine, allergen, or cold air. Secondary measures included symptom scores, need for rescue doses, and patient preference. Salmeterol is a selective, beta 2-agonist that has been studied in the treatment of exercise-induced, nocturnal, and allergen-induced asthma. Salmeterol interacts with the traditional beta-receptor in a similar manner as other beta-agonists, and it exhibits potent in vitro antiinflammatory effects as an inhibitor of inflammatory mediator release. Less evidence exists for its in vivo antiinflammatory activity. Salmeterol demonstrates prolonged receptor occupancy, which is thought to contribute to its long duration of action. The recommended dose is 50 micrograms via metered-dose inhaler or dry-powdered inhalation. In the published clinical trials, salmeterol was more effective than albuterol in treating asthma, including exercise and allergen-induced asthma. Salmeterol's major advantage over other inhaled beta-agonists is its long duration of action (12 hours), making it an excellent choice for treatment of nocturnal asthma. A potential disadvantage is delayed onset of action. Tachyphylaxis to salmeterol's bronchodilator effects has not been shown, but tolerance to its protective effects against methacholine-induced bronchoconstriction has occurred. Adverse effects reported have been mild and have included headache, tremor, and palpitations. Salmeterol is an effective beta 2-agonist in the treatment of asthma. However, several issues require further investigation regarding its long-term effects on disease control, significance of antiinflammatory activity, and role as a rescue medication.
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