Influence of particle size on lung deposition and pharmacokinetics of beclomethasone dipropionate in children.

ABSTRACT

We set out to evaluate lung deposition, systemic availability, and basic pharmacokinetic parameters of beclomethasone dipropionate (BDP) in children with chronic asthma. Plasma levels of BDP, 17 and 21 beclomethasone monopropionate (17-BMP and 21-BMP), and beclomethasone were measured after an intravenous infusion of 60 microg BDP and after inhalation of A) 100 microg HFA-BDP, B) 200 microg HFA-BDP, C) 200 microg HFA-BDP after ingestion of charcoal to block gastrointestinal (GI) absorption of drug, and D) 400 microg CFC-BDP. A breath-actuated pMDI (Autohaler) was used for HFA inhalations, and a pMDI with a large volume spacer (Volumatic) for CFC inhalations. Treatments A-D were given in a randomized, cross-over design. Fourteen patients aged 10-14 years completed all 5 study days. The mean systemic bioavailabilities in percent of dose leaving the canister valve (ex-valve) were 70% (100 HFA), 74% (200 HFA), 60% (200 HFA + charcoal), and 27% (400 microg CFC). After HFA treatment, 82% of the systemically available dose was absorbed through the lungs, and 18% from the gastrointestinal tract. The estimated bioavailability of BDP from the GI tract was 68%. BDP was metabolized to 17-BMP within minutes. Mean steady-state volume of distribution of 17-BMP was 84 L, and the mean terminal half-life (T((1/2))) after the four inhalations was 2.7 hr (range, 2.2-3.7 hr). Mean T((1/2)) and clearance after i.v. administration were 1.7 hr and 0.9 L/min, respectively. The HFA Autohaler delivers approximately three times as much BDP to the intrapulmonary airways as a CFC-pMDI with a large volume spacer.