Regional lung deposition of a technetium 99m-labeled formulation of mometasone furoate administered by hydrofluoroalkane 227 metered-dose inhaler.
BACKGROUND
A new inhaled suspension formulation of mometasone furoate (MF), a potent corticosteroid with minimal systemic availability, has been developed for the treatment of asthma. This formulation is delivered by metered-dose inhaler (MDI) using the nonchlorofluorocarbon propellant hydrofluoroalkane 227 (HFA-227).


OBJECTIVE
The primary goal of this study was to determine the respiratory tract deposition of this formulation of MF. A secondary objective was to measure plasma concentrations of MF and a putative metabolite, 6-X-OH MF, to determine the systemic exposure to corticosteroid.


METHODS
This was a single-dose, open-label study in which 200 microg of technetium 99m (99mTc)-radiolabeled MF was administered to patients with asthma. Gamma scintigraphy was used to quantify lung, oropharyngeal, stomach, and MDI mouthpiece deposition patterns of MF.


RESULTS
Eleven patients, aged 21 to 47 years, with a history of asthma were enrolled in and completed the study. The mean (+/- SD) whole lung deposition of MF was 13.9%+/-5.7% of the metered (ex-valve) dose. The central lung zone received 5.3%+/-2.8% of the dose; the intermediate zone received 4.7%+/-1.9%; and peripheral lung deposition was 4.0%+/-1.5%. The mean (+/- SD) ratio of peripheral to central lung deposition was 0.8+/-0.2. Oropharyngeal deposition was 79.1%+/-8.7% of the ex-valve dose, with 6.3%+/-7.8% deposited on the MDI mouthpiece and 0.7%+/-0.5% exhaled. The majority of plasma samples taken for analysis of MF and 6-13-OH MF concentrations were below the limit of quantification (50 pg/mL) in all patients after inhalation of 200 microg 99mTc-labeled ME CONCLUSION: The lung deposition of MF when administered via HFA-227 MDI is comparable to the 10 to 20% lung deposition seen with other corticosteroid suspension for- mulations administered by MDI that have demonstrated effectiveness in the treatment of asthma.
Pickering
H
H
Pharmaceutical Profiles Ltd, Nottingham, United Kingdom.
Pitcairn
G R
GR
Hirst
P H
PH
Bacon
P R
PR
Newman
S P
SP
Affrime
M B
MB
Marino
M
M
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001249:Asthma / Q000378:metabolism; D049669:History, 16th Century; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008875:Middle Aged; D000068656:Mometasone Furoate; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011244:Pregnadienediols / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging
D000305:Adrenal Cortex Hormones; D015609:Organotechnetium Compounds; D011244:Pregnadienediols; D000068656:Mometasone Furoate