Comparative pulmonary function and pharmacokinetics of fluticasone propionate and salmeterol xinafoate delivered by two dry powder inhalers to patients with asthma.

摘要

BACKGROUND: This report presents results of the first human study of a new dry powder inhaler (DPI-C). DPI-C uses reverse flow cyclone technology to retain larger particles in the device and to increase efficiency of respirable drug release. The study was conducted to determine comparative pharmacokinetics (not bioequivalence) of DPI-C and DPI-A (Advair Diskus(R), GlaxoSmithKline) and to establish preliminary efficacy and safety of DPI-C. METHODS: Nineteen patients with mild-moderate asthma received two treatments (randomized crossover design). Treatments were one inhalation from DPI-A labeled to deliver 100 mug fluticasone propionate and 50 mug salmeterol, or one inhalation from DPI-C which contained approximately 10% less of each drug per metered dose. Prior to dosing, 10 g of charcoal was administered. FEV1 increase over baseline (measured over 12 h), plasma concentrations of fluticasone and salmeterol (measured over 12.5 h), and occurrence of adverse events were the primary measures of device performance and safety. RESULTS: Seventeen patients were evaluable. Response profiles of percent increase in FEV1 over baseline showed no statistically significant differences between devices. Peak plasma concentrations of both fluticasone (p=0.003) and salmeterol (p=0.084) were higher from DPI-C. Mean extent of absorption [area under the curve (AUC)] of fluticasone was approximately 30% greater with DPI-C, whereas AUC of salmeterol was approximately 40% greater with DPI-A. CONCLUSIONS: DPI-C provided similar improvement in pulmonary function compared with DPI-A. Pharmacokinetic results showed a greater initial absorption of salmeterol with DPI-C but greater continued absorption and a 40% greater AUC with DPI-A, which we attribute to slower but more extensive oral absorption because of the greater mass of swallowed large particles of salmeterol generated by DPI-A. No patient reported any treatment-related adverse event or use of rescue medication during this study. Determination of the significance of the observed differences in pharmacokinetics from this single-dose study requires further exploration in studies using clinically relevant dosing regimens.