Back to the Top
Dear sir,
If the oral clearance exeeds the hepatic blood flow rate it suggests
that the drug has high clearance. But, can it also suggest that the
drug is poorly absorbed from GIT due to poor aqueous solubility or the
drug is going extensive first pass/presystemic elimination.
Kindly comment.
Jawahar Lal
Back to the Top
The following message was posted to: PharmPK
Dear Jawaher,
The bioavailability term (F) in the Oral clearance (CL/F) is affected
by everything that might happen to the drug from gut to site of
measurement. If a drug undergoes chemical degredation in the
stomach/gut, is poorly absorbed, metabolizaed in gut membrane, or
metabolized in liver, less wil be available and thus your oral CL will
become a larger number.
Toufigh Gordi
Back to the Top
Hello Dr. Jawahar,
Since the clearance (CL/F) value becomes larger and larger as the F
becomes smaller. I do not think that u can classify whether a drug has
high clearance or not just based on the value obtained from "oral
clearance". It could possibly be that your drug has either low
bioavailability (could be any of the reasons u mentioned) or a high
clearance and high bioavailability. Bioanalytical quantification would
become a big issue in case of poor bioavailability and high clearance.
why do you not get the estimate of clearance following intravenous
admnistration of the drug. It will make things clear and probably
answer your question.
You could also do a portal-venous collection following oral
administration to delineate the role of liver in the clearance.
regards
Raj
Rajanikanth M
Post Doc Assoc
Pharmaceutics Division
University of Florida
Gainesville
Back to the Top
Dear Gordi and Rajanikanth,
I agree with your comments on CL/F.
I have one doubt, if in case Bioavailability of the compound is good
(say for ex, f ~ 100%), could it be possible that this particular
compound is undergoing extrahepatic clearance (i.e., Renal Clearance)?
And yes as suggested by rajanikanth once we have IV data it will
clarify the doubt completely.
Thanks,
B.L.Suresh
Back to the Top
The following message was posted to: PharmPK
Dear Suresh,
There are 2 points in your statement:
> in case Bioavailability of the compound is good (say
> for ex, f ~ 100%), could it be possible that this particular compound
> is
> undergoing extrahepatic clearance (i.e., Renal Clearance)?
If the bioavailability is close to 100%, then your oral clearance
(CL/F) will be very similar to the total CL. The latter is estimated
after iv dose.
The second point is that a high oral bioavailability does not
necessarily imply the compound is not metabolized or is only eliminated
through excretion via kidneys. The fraction metabolized (fm) does not
need to have any significant impact on the bioavailability. You may
have a compound eliminated solely through hepatic metabolism but high
bioavailability. The elimination process might be very slow and thus
have no contribution on its first-pass and bioavailability.
Toufigh Gordi , PhD
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)