Deposition, imaging, and clearance: what remains to be done?
Deposition and clearance studies are used during product development and in fundamental research. These studies mostly involve radionuclide imaging, but pharmacokinetic methods are also used to assess the amount of drug absorbed through the lungs, which is closely related to lung deposition. Radionuclide imaging may be two-dimensional (gamma scintigraphy or planar imaging), or three-dimensional (single photon emission computed tomography and positron emission tomography). In October 2009, a group of scientists met at the "Thousand Years of Pharmaceutical Aerosols" conference in Reykjavik, Iceland, to discuss future research in key areas of pulmonary drug delivery. This article reports the session on "Deposition, imaging and clearance." The objective was partly to review our current understanding, but more importantly to assess "what remains to be done?" A need to standardize methodology and provide a regulatory framework by which data from radionuclide imaging methods could be compared between centers and used in the drug approval process was recognized. There is also a requirement for novel radiolabeling methods that are more representative of production processes for dry powder inhalers and pressurized metered dose inhalers. A need was identified for studies to aid our understanding of the relationship between clinical effects and regional deposition patterns of inhaled drugs. A robust methodology to assess clearance from small conducting airways should be developed, as a potential biomarker for therapies in cystic fibrosis and other diseases. The mechanisms by which inhaled nanoparticles are removed from the lungs, and the factors on which their removal depends, require further investigation. Last, and by no means least, we need a better understanding of patient-related factors, including how to reduce the variability in pulmonary drug delivery, in order to improve the precision of deposition and clearance measurements.
Activaero GmbH, Gemünden, Germany.
Gerhard
G
Scheuch
William
W
Bennett
Lars
L
Borgström
Andy
A
Clark
Richard
R
Dalby
Myrna
M
Dolovich
John
J
Fleming
Peter
P
Gehr
Igor
I
Gonda
Chris
C
O'Callaghan
Glyn
G
Taylor
Steve
S
Newman
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D009330:Nebulizers and Vaporizers; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011877:Radionuclide Imaging / Q000379:methods; D012106:Research / Q000639:trends; D014018:Tissue Distribution
D000336:Aerosols; D004364:Pharmaceutical Preparations