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

Background: To improve dosing consistency and product features, budesonide inhalation powder delivered via a dry powder inhaler (DPI) (DPI-A* 200 mu g) was redesigned to include lactose, a newly shaped mouthpiece, and a new dose indicator (DPI-B dagger). Budesonide CPI-B is available in two strengths (90 mu g, 180 mu g). 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 mu g x 4 inhalations, budesonide DPI-B 180 mu g x 4 inhalations, or budesonide DPI-B 90 mu g x 8 inhalations, on 3 days, each separated by a washout period of >= 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 (Cls) for their AUC(0-infinity) and C-max ratios fell between 80 and 125%. Adverse events were collected. Results: The 90% Cls for the ratios of AUC(0-infinity) and C-max for budesonide DPI-A 200 mu g and DPI-B 180 mu g and for both budesonide DPI-B strengths fell between 80% and 125% (AUC(0-infinity): budesonide DPI-B 180 mu g x 4/DPI-A 200 mu g x 4: 96.3% [90% Cl: 90.9,102,1]; budesonide DPI-B 180 mu g x 4/DPI-B 90 mu g x 8: 92.2% [90% Cl: 87.0, 97.7]; C-max: (budesonide DPI-B 180 mu g x 4/DPI-A 200 mu g x 4:100.4% [95% Cl: 92.1, 109.4]; budesonide DPI-B 180 mu g x 4/DPI-B 90 mu g x 8: 94.4% [90% Cl: 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 mu g and CPI-B 180 mu g have systemic absorption bioequivalence, and DPI-B 90 mu g and 180 mu g 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 >= 19 years.