Evidence of the in vivo esterification of budesonide in human airways.
OBJECTIVE
Budesonide, unlike fluticasone propionate, undergoes fatty acid esterification in the lungs, and there is a need to characterize fully the distribution and fate of the two drugs after inhalation in humans.


METHODS
This open-label, randomized study was performed in adults undergoing whole lung or lobar resection resulting from lung cancer. Patients were given single 1000-mug doses of both budesonide and fluticasone propionate via dry powder inhalers before surgery. Tissue samples from peripheral and central lung, an ex vivo bronchial brush sample and intercostal muscle, together with plasma samples, were taken during surgery and analysed by liquid chromatography plus tandem mass spectrometry.


RESULTS
Lung tissue samples were obtained from 22 patients at surgery, 1-43 h after drug dosing. Budesonide was detectable from earliest sampling in central and peripheral lung tissue up to 10 h (in six of 22 samples), fluticasone propionate up to 22 h after inhalation (in 16 of 22 samples), and budesonide oleate up to 43 h after inhalation (in 21 of 22 samples). Budesonide, but not fluticasone propionate, was detected in intercostal muscle for up to 10 h after inhalation. Bronchial brush samples showed the presence of fluticasone propionate for up to 18 h, suggesting the presence of undissolved drug powder particles in the airway lumen.


CONCLUSIONS
Sustained retention of esterified budesonide in the lungs supports the prolonged duration of action of budesonide and suitability for once-daily administration.
van den Brink
Karen I Maassen
KI
Department of Respiratory Medicine, Academic Hospital, Maastricht, The Netherlands.
Boorsma
Martin
M
Staal-van den Brekel
A Jeske
AJ
Edsbäcker
Staffam
S
Wouters
Emiel F
EF
Thorsson
Lars
L
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000378:metabolism; D019819:Budesonide / Q000008:administration & dosage* / Q000378:metabolism; D004951:Esterification / Q000187:drug effects*; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000730:Androstadienes; D019819:Budesonide; D000068298:Fluticasone