Relative systemic availability of budesonide in patients with asthma after inhalation from two dry powder inhalers.

摘要

BACKGROUND: To improve dosing consistency and product features, budesonide inhalation powder delivered via a dry powder inhaler (DPI) (DPI-A 200 microg) was redesigned to include lactose, a newly shaped mouthpiece, and a new dose indicator (DPI-B). Budesonide DPI-B is available in two strengths (90 microg, 180 microg). OBJECTIVE: To compare the relative rate and extent of the systemic availability of budesonide inhaled via DPI-A and DPI-B and test for systemic absorption bioequivalence. METHODS: Adults (n = 37) with asthma as defined by the American Thoracic Society were randomized in an open-label, crossover, single-center, single-dose study to budesonide DPI-A 200 microg x 4 inhalations, budesonide DPI-B 180 microg x 4 inhalations, or budesonide DPI-B 90 microg x 8 inhalations, on 3 days, each separated by a washout period of >or= 5 days. Plasma samples were collected immediately before and up to 12 h after dosing. Primary pharmacokinetic variables were area under the drug plasma concentration-time curve from 0 to infinity (AUC(0-infinity)) and maximum plasma concentration (C(max)); plasma concentration at 12 h (C(12h)) and time to maximum plasma concentration (T(max)) were secondary variables. Treatments were considered bioequivalent if the 90% confidence intervals (CIs) for their AUC(0-infinity) and C(max) ratios fell between 80 and 125%. Adverse events were collected. RESULTS: The 90% CIs for the ratios of AUC(0-infinity) and C(max) for budesonide DPI-A 200 microg and DPI-B 180 microg and for both budesonide DPI-B strengths fell between 80% and 125% (AUC(0-infinity): budesonide DPI-B 180 microg x 4/DPI-A 200 microg x 4: 96.3% [90% CI: 90.9, 102.1]; budesonide DPI-B 180 microg x 4/DPI-B 90 microg x 8: 92.2% [90% CI: 87.0, 97.7]; C(max): (budesonide DPI-B 180 microg x 4/DPI-A 200 microg x 4: 100.4% [95% CI: 92.1, 109.4]; budesonide DPI-B 180 microg x 4/DPI-B 90 microg x 8: 94.4% [90% CI: 86.6, 102.9]). No differences in C(12h) and T(max) were found between treatments. All treatments were well tolerated. CONCLUSIONS: Budesonide DPI-A 200 mug and DPI-B 180 mug have systemic absorption bioequivalence, and DPI-B 90 microg and 180 microg are dose-strength equivalent when administered at the same dose. These results may not be generalized to all patients with asthma, as this analysis included only patients with mild-to-moderate asthma aged >or= 19 years.