Urinary Pharmacokinetic Methodology to Determine the Relative Lung Bioavailability of Inhaled Beclometasone

Urinary pharmacokinetic methods have been introduced to identify the relative lung and systemic availability of inhaled drugs but have not been extended to corticosteroids. The main aims were to validate the urinary pharmacokinetic methodology when applied to inhaled beclometasone dipropionate (BDP), demonstrate the usefulness of the method and compare its indices to the in-vitro characteristics of the emitted dose. A simple and sensitive LC-MS method for quantifying BDP and its metabolites in methanol (for in-vitro studies) and urine samples was identified and validated in accordance with the FDA and ICH guidelines. The accuracy, precision, and recovery of the method were within acceptable limits (±15%). Twelve healthy volunteers completed the in-vivo urinary pharmacokinetic validation of the methodology to determine the relative lung bioavailability of inhaled beclometasone following inhalation. Twelve healthy volunteers received randomised doses, separated by >7 days, of 2000μg BDP solution with (OralC) and without (Oral) 5g oral charcoal, ten 100μg inhalations from a Qvar® Easi breathe metered dose inhaler (pMDI) with (QvarC) and without (Qvar) oral charcoal and eight 250μg inhalations from a Clenil® pMDI (Clenil). Subjects provided urine samples at 0, 0.5, 1, 2, 3, 5, 8, 12, and 24 hours post study dose. Urinary concentrations of BDP and its metabolites, 17-beclometasone monopropionate (BMP) and beclometasone (BOH) were measured. No BDP, BMP, or BOH was detected in any samples post OralC dosing. Post oral dosing, no BDP was detected in any of the urine samples and no BMP or BOH was excreted in the first 30 minutes. Significantly more (p