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The following message was posted to: PharmPK
Sandeep,
The AUCpo/AUCiv should be equal to the fraction absorbed
into the circulation by either the IP or oral route. A low
fraction absorbed by oral route could indicate first pass
metabolism. If the fraction absorbed by IP route is also low,
then first pass metabolism would be more likely. However,
incomplete oral absorption could also be a result of gut wall
metabolism, and/or poor drug dissolution/absorption. In addition,
anatomical differences between species could influence the
variance observed in fraction absorbed by the IP route.
Calculating the hepatic extraction ratio could be a method
of determining first pass metabolism while circumventing the
problems of gut wall metabolism, poor dissolution/absorption, and
interspecies differences.
Cl(hepatic)= Q*ER equation 1
Cl= D/AUCiv equation 2
F= 1-ER= 1- Q*ER/Q = 1- CL/Q= 1- D/Q*AUCiv equation 3
F= Q/[Q+ D/AUCoral] equation 4
By substituting an appropriate values of Q (hepatic blood flow)
into equation 3, the availability of the drug (F) can determined
from the AUCiv. The AUCoral can also be used to determine the
systemic bioavailability by equation 4.
Mike Leibold, PharmD, RPh
ML11439.aaa.goodnet.com
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)