Lung deposition of inhaled drugs increases with age

Budesonide plasma concentrations after inhalation of a fixed dose of the drug from a pressurized metered dose inhaler (pMDI) with spacer (Nebuchamber) were compared in young children and adults: 26 patients with mild asthma comprising 8 children 2-3 yr, 8 children 4-6 yr, and 10 adults 20-41 yr. Budesonide 2 x 200 microg was given by pMDI via Nebuchamber with mouthpiece and noseclip. Children of 2-3 yr used a facemask. Plasma was collected regularly for 8 h after drug administration. Budesonide was measured by liquid chromatography plus tandem mass spectrometry. The dose to patient was estimated as the dose of budesonide delivered from the pMDI with adapter minus the amount of budesonide recovered from the spacer, facemask, or mouthpiece, mouth rinse, and facial skin. The systemic exposure was estimated from the plasma concentration and expressed as the area under the curve of plasma concentration versus time (AUC). Terminal half-life (T(1/2)) was evaluated. Dose to patient, AUC, and T(1/2) were similar in the three age groups (p > 0.35). Nebuchamber delivers the same dose of budesonide to young children and adults. Yet the plasma concentration of budesonide was similar in young children and adults. Therefore, lung dose is increased with age. This suggests that from a safety perspective, the prescribed dose of budesonide inhaled from a pMDI with Nebuchamber spacer need not be adjusted for age or use of facemask. Children and adults can use the same nominal dose of budesonide via Nebuchamber as adults without an increased risk of systemic exposure.