Pharmacokinetics of a novel submicron budesonide dispersion for nebulized delivery in asthma

The objective of this study was to evaluate the safety and pharmacokinetics of unit dose budesonide (UDB), an aqueous dispersion of submicron-sized budesonide particles, and a commercially available budesonide suspension formulation. This was a randomized, double-blind, active-controlled, 4-period, 4-way crossover trial in 16 healthy, adult volunteers. Subjects received UDB 0.24, 0.12, and 0.06 mg or commercial budesonide 0.25 mg via a jet nebulizer. Tmax was significantly (p < 0.05) earlier for UDB 0.06, 0.12, and 0.24 mg (4.5 ± 3.3, 3.1 ± 1.5, 3.7 ± 1.5 min) vs. commercial budesonide (9.1 ± 7.1 min). Cmax was significantly (p < 0.05) higher for UDB 0.24 mg vs. commercial budesonide 0.25 mg (434.5 ± 246.9 pg/mL vs. 303.5 ± 177.4 pg/mL) but not between UDB 0.12 mg (239.9 ± 140 pg/mL) and commercial budesonide 0.25 mg (p = 0.448). AUC0–∞ was marginally, but significantly lower for UDB 0.24 mg than commercial budesonide 0.25 mg. AUCs for UDB 0.12 mg were lower than commercial budesonide 0.25 mg. UDB 0.24 mg was absorbed more rapidly and achieved higher peak concentrations than commercial budesonide 0.25 mg, but had a lower AUC0–∞. UDB 0.12 mg also was absorbed more rapidly but had lower Cmax and AUCs than commercial budesonide 0.25 mg.