Urinary pharmacokinetic methodology to determine the relative lung bioavailability of inhaled beclometasone dipropionate

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Urinary pharmacokinetic methodology can be used to identify the relative bioavailability to the lungs and the systemic circulation after an inhalation but has not yet been extended to corticosteroids. • Two (Qvar® and Clenil®) HFA (CFC‐free) metered dose inhaler formulations of beclometasone dipropionate are now available. The recommended dose of Qvar is half that of Clenil but the two have yet to be compared. WHAT THIS STUDY ADDS • The urinary excretion of beclometasone dipropionate and its main metabolites (beclometasone‐17‐ monopropionate and beclometasone) in the first 30 min post inhalation represents the relative bioavailability to the lungs after an inhalation. • Similarly the 24 h urinary excretion of the main metabolites can be used to identify the relative bioavailability to the systemic circulation after an inhalation. he relative lung and systemic bioavailability between Qvar and Clenil confirms the two fold difference in their recommended doses. AIM Urinary pharmacokinetic methods have been identified to determine the relative lung and systemic bioavailability after an inhalation. We have extended this methodology to inhaled beclometasone dipropionate (BDP). METHOD Ethics Committee approval was obtained and all subjects gave consent. Twelve healthy volunteers received randomized doses, separated by >7 days, of 2000 µg BDP solution with (OralC) and without (Oral) 5 g oral charcoal, 10 100 µg inhalations from a Qvar® Easibreathe metered dose inhaler (pMDI) with (QvarC) and without (Qvar) oral charcoal and eight 250 µg inhalations from a Clenil® pMDI (Clenil). Subjects provided urine samples at 0, 0.5, 1, 2, 3, 5, 8, 12 and 24 h post study dose. Urinary concentrations of BDP and its metabolites, beclometasone‐17‐monopropionate (17‐BMP) and beclometasone (BOH) were measured. RESULTS No BDP, 17‐BMP or BOH were detected in any samples post OralC dosing. Post oral dosing no BDP was detected in all urine samples and no 17‐BMP or BOH was excreted in the first 30 min. Significantly more (P < 0.001) BDP, 17‐BMP and BOH were excreted in the first 30 min and the cumulative 24 h urinary excretions post Qvar and Clenil compared with Oral. The mean ratio (90% confidence interval) of the 30 min urinary excretions for Qvar compared with Clenil was 231.4 (209.6, 255.7) %. CONCLUSION The urinary pharmacokinetic methodology to determine the relative lung and systemic bioavailability post inhalation, using 30 min and cumulative 24 h post inhalation samples, applies to BDP. The ratio between Qvar and Clenil is consistent with related clinical and lung deposition studies.