High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma.
OBJECTIVE
To examine the deposition and pharmacokinetics of ciclesonide administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) in patients with asthma.


METHODS
Twelve patients with mild asthma (FEV1, 95% predicted) inhaled a single dose of 99mtechnetium (Tc)-ciclesonide 320 microg ex-actuator (400 microg ex-valve). Deposition of ciclesonide in the lung and oropharynx was quantified using two-dimensional (2D)-gamma scintigraphy. Three-dimensional single photon emission computed tomography (3D SPECT) was used to assess the regional distribution of ciclesonide in the lung. The pharmacokinetics of ciclesonide and its active metabolite, desisobutyryl-ciclesonide (des-CIC), were determined by liquid chromatography-tandem mass spectrometry. Ciclesonide and des-CIC concentrations were determined in mouth-rinsing solutions.


RESULTS
2D-gamma scintigraphy indicated that ciclesonide deposition was higher in the whole lung (52%) than in the oropharynx (32.9%). Furthermore, 3D SPECT revealed that ciclesonide deposition within the lungs was highest in the peripheral regions that contain the small airways and alveoli. The pharmacokinetic profile of Tc-labeled ciclesonide and des-CIC was similar to that obtained after inhalation of non-labeled formulations in previous studies. Des-CIC accounted for 14.9% of the total molar concentration of ciclesonide/des-CIC in mouth-rinsing solutions obtained between 7 and 12min after inhalation.


CONCLUSIONS
Inhalation of ciclesonide via HFA-MDI results in high pulmonary deposition, especially in the peripheral regions of the lung. High pulmonary deposition contributes to ciclesonide's ability to maintain lung function and control symptoms in patients with asthma. Deposition and activation of ciclesonide in the oropharynx is low, consistent with previous reports of low oropharyngeal deposition and a reduced incidence of local side effects in patients receiving ciclesonide therapy.
Newman
Steve
S
Pharmaceutical Profiles, Nottingham, UK.
Salmon
Andrew
A
Nave
Ruediger
R
Drollmann
Anton
A
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015331:Cohort Studies; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D009960:Oropharynx / Q000000981:diagnostic imaging / Q000378:metabolism*; D011282:Pregnenediones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013667:Technetium / Q000008:administration & dosage / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D001993:Bronchodilator Agents; D011282:Pregnenediones; D013667:Technetium; C494355:desisobutyrylciclesonide; C120481:ciclesonide