SALMETEROL - A NOVEL, LONG-ACTING BETA(2)-AGONIST

OBJECTIVE: The clinical pharmacology, pharmacokinetics, clinical effic acy, and adverse effects of the long-acting beta(2)-agonist salmeterol are reviewed. DATA SOURCES: A MEDLINE search was performed to identif y English-language publications pertaining to salmeterol. STUDY SELECT ION: Open and controlled trials were reviewed in assessing clinical ef ficacy. Only the results of controlled, randomized trials were conside red in the effectiveness evaluation. DATA EXTRACTION: The primary meas ures of effectiveness in the clinical trials were bronchodilator activ ity and reduction of hyperresponsiveness that may reflect antiinflamma tory activity. Bronchodilator activity was measured as changes in pulm onary function; reduction of hyperresponsiveness was evaluated using r espiratory challenge with methacholine, histamine, allergen, or cold a ir. Secondary measures included symptom scores, need for rescue doses, and patient preference. DATA SYNTHESIS: Salmeterol is a selective, be ta(2)-agonist that has been studied in the treatment of exercise-induc ed, nocturnal, and allergen-induced asthma Salmeterol interacts with t he traditional beta-receptor in a similar manner as other beta-agonist s, and it exhibits potent in vivo antiinflammatory effects as an inhib itor of inflammatory mediator release. Less evidence exists for its in vivo antiinflammatory activity. Salmeterol demonstrates prolonged rec eptor occupancy, which is thought to contribute to its long duration o f action. The recommended dose is 50 mu g via metered-dose inhaler or dry-powdered inhalation. In the published clinical trials, salmeterol was more effective than albuterol in treating asthma, including exerci se and allergen-induced asthma. Salmeterol's major advantage over othe r inhaled beta-agonists is its long duration of action (12 hours), mak ing it an excellent choice for treatment of nocturnal asthma. A potent ial disadvantage is delayed onset of action. Tachyphylaxis to salmeter ol's bronchodilator effects has not been shown, but tolerance to its p rotective effects against methacholine-induced bronchoconstriction has occurred. Adverse effects reported have been mild and have included h eadache, tremor, and palpitations.