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Pharmacokinetics Salmeterol xinafoate, an ionic salt, dissociates in solution so that the salmeterol and 1-hydroxy-2-naphthoic acid (xinafoate) moieties are absorbed, distributed, metabolized, and excreted independently. Salmeterol acts locally in the lung; therefore, plasma
levels do not predict therapeutic effect. Absorption Text Continues Below
Because of the small therapeutic dose, systemic levels of salmeterol are low or undetectable after inhalation of recommended doses (42 mcg of salmeterol inhalation aerosol twice daily). Following chronic administration of an inhaled dose of 42 mcg twice daily, salmeterol was detected in plasma within 5 to 10 minutes in 6 patients with asthma; plasma concentrations were very low, with peak concentrations of 150 pg/mL and no accumulation with repeated doses. Larger inhaled doses gave approximately proportionally increased blood levels.
In these patients, a second peak concentration of 115 pg/mL occurred at about 45 minutes, probably due to absorption of the swallowed portion of the dose (most of the dose delivered by a metered-dose inhaler is swallowed). Distribution Binding of salmeterol to human plasma proteins averages 96% in vitro over the concentration range of 8 to 7,722 ng of salmeterol base per milliliter, much higher than those achieved following therapeutic doses of salmeterol. Metabolism Salmeterol base is extensively metabolized by hydroxylation, with subsequent elimination predominantly in the feces. No significant amount of unchanged salmeterol base was detected in either urine or feces. Excretion In 2 healthy subjects who received 1 mg of radiolabeled salmeterol (as salmeterol xinafoate) orally, approximately 25% and 60% of the radiolabeled salmeterol was eliminated in urine and feces, respectively, over a period of 7 days. The terminal elimination half-life was about 5.5 hours (1 volunteer only). Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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