Back to the Top
Hello All:
We have conducted radiolabeled ADME studies in rats for a compound
and found that approximately 20% of the orally administered
radioactivity was recovered in expired air. We are now planning to
conduct a human ADME study on the same compound and have included in
the protocol sampling of breath at 10 timepoints between 1 and 24
hours post dosing and once a day after the first 24 hours until the
radioactivity is undetectable. I would appreciate any input from
members who have analyzed data from a study similar to this, where a
significant percent of the radiolabeled dose was recovered in expired
air. How were the data from expired air analyzed and total recovery
calculated? What are some of the things I should watch out for?
Thanks
Girish
Back to the Top
The following message was posted to: PharmPK
Hi Girish,
An approach would be to sample CO2 with Douglas Bags at specific
times to generate a plot of 14CO2 expiration-rate (DPM/min) versus
time. Integrating such a plot (like calculating AUC) would yield the
estimated total amount of radioactivity expired. This way your
patients don't need to breath into a Douglas bag for extended periods
of time (not very appealing to IRB's ;-) See also:
Beumer JH, Beijnen JH, Schellens JH.
Mass balance studies, with a focus on anticancer drugs.
Clin Pharmacokinet. 2006;45(1):33-58.
PMID: 16430310 [PubMed - in process]
Regards, Jan
Jan Hendrik Beumer
Pharm.D., Ph.D.
Post-Doctoral Associate
The Hillman Cancer Center
Research Pavilion, G.28
5117 Centre Avenue
Pittsburgh, PA 15213-1863
Tel.: +1-412-623-3238
Fax.: +1-412-623-1212
Email: beumerjh.-a-.upmc.edu
Back to the Top
My suggestion would be to put the label in a less liable postion. If
you do this will have to re-run your ADME in rat before do human
AMDE. If you don't I am afraid your data might not be usable for
submission. I am assuming you are using 14-C as your label.
Stanley Cotler
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)