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

Author(s): Shrewsbury SB, Bosco AP, Uster PS

Affiliation(s): MAP Pharmaceuticals Inc., Mountain View, CA, USA.

Publication date & source: 2009-01-05, Int J Pharm., 365(1-2):12-7. Epub 2008 Aug 22.

Publication type:

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 0.06mg or commercial budesonide 0.25mg via a jet nebulizer. T(max) was significantly (p<0.05) earlier for UDB 0.06, 0.12, and 0.24mg (4.5+/-3.3, 3.1+/-1.5, 3.7+/-1.5min) vs. commercial budesonide (9.1+/-7.1min). C(max) was significantly (p<0.05) higher for UDB 0.24mg vs. commercial budesonide 0.25mg (434.5+/-246.9pg/mL vs. 303.5+/-177.4pg/mL) but not between UDB 0.12mg (239.9+/-140pg/mL) and commercial budesonide 0.25mg (p=0.448). AUC(0-infinity) was marginally, but significantly lower for UDB 0.24mg than commercial budesonide 0.25mg. AUCs for UDB 0.12mg were lower than commercial budesonide 0.25mg. UDB 0.24mg was absorbed more rapidly and achieved higher peak concentrations than commercial budesonide 0.25mg, but had a lower AUC(0-infinity). UDB 0.12mg also was absorbed more rapidly but had lower C(max) and AUCs than commercial budesonide 0.25mg.