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

ABSTRACT

Background: To improve dosing consistency and product features, budesonide inhalation powder delivered via a dry powder inhaler (DPI) (DPI?A^* 200?μg) 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?μg, 180?μg).

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?μg × 4 inhalations, budesonide DPI?B 180?μg × 4 inhalations, or budesonide DPI?B 90?μg × 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–∞) 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–∞ and C_max ratios fell between 80 and 125%. Adverse events were collected.

Results: The 90% CIs for the ratios of AUC_0–∞ and C_max for budesonide DPI?A 200?μg and DPI?B 180?μg and for both budesonide DPI?B strengths fell between 80% and 125% (AUC_0–∞: budesonide DPI?B 180?μg × 4/DPI?A 200?μg × 4: 96.3% 90 % CI: 90.9, 102.1]; budesonide DPI?B 180?μg × 4/DPI?B 90?μg × 8: 92.2% 90 % CI: 87.0, 97.7]; C_max: (budesonide DPI?B 180?μg × 4/DPI?A 200?μg × 4: 100.4% 95 % CI: 92.1, 109.4]; budesonide DPI?B 180?μg × 4/DPI?B 90?μg × 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?μg and DPI?B 180?μg have systemic absorption bioequivalence, and DPI?B 90?μg and 180?μg 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.