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


METHODS
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) %.


CONCLUSIONS
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.
Division of Pharmacy and Pharmaceutical Sciences, School of Applied Sciences, University of Huddersfield, UK.
Amira S A
AS
Said
Lindsay P
LP
Harding
Henry
H
Chrystyn
D000280:Administration, Inhalation; D000328:Adult; D001507:Beclomethasone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D001682:Biological Availability; D002606:Charcoal / Q000008:administration & dosage*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D013997:Time Factors; D014018:Tissue Distribution; D055815:Young Adult
D005938:Glucocorticoids; D002606:Charcoal; C065857:beclomethasone 17-monopropionate; D001507:Beclomethasone