Back to the Top
The following message was posted to: PharmPK
Dear All,
For a biopharmaceutical classification class one drug which is
highly soluble and highly permeable,what could be the reasons
for:
1. Drug AUC of reference sample is greater than test sample,
whereas AUC of metabolite of test sample is greater than that of
the reference
sample.
Thankyou
Sincerely
Kiran S Lagu
Back to the Top
The following message was posted to: PharmPK
There are two possible explanations
First one is that you have a different fraction
absorbed from reference and test.
If bioavailbility is F=AUCoral/AUCiv=fa*fe where fa is
fraction absorbed and fe is fraction escaping first
pass effects.
Imagine that your test sample has fa=0.8 and fe=0.7 so
F= 0.56
Assuming no other presystemic looses apart from
metabolism., from a dose of 100 mg, 56 mg will reach
unaltered the systemic circulation and the other 44
will be metabolized.
If your reference has fa=0.9 and fe=0.7 your F will
be F=0.63. from a dose of 100 mg, 63 reach systemic
circulation and 39 are metabolized.
So you have bigger AUC for drug Reference (with lower
AUC for metabolite) and lower AUC for Test (with
bigger AUC for metabolite)
If the drug is really HS-HP…well…it is difficult to
expect that the formulation could lead to a big
difference in fa…(is dissolution in vitro similar in
both cases????)
Second explanation
assuming same fa (same fraction in magnitude), the
only reason for expecting a different fe is a big
difference in absorption RATE…that could lead to a
saturation of metabolic systems and thus to a change
in the fraction escaping first pass.
If the profile of the test shows a slower input rate,
maybe the fe is lower (less drug escapes from first
pass)..so more drug is metabolized from test
formulation and the AUC for metabolite would be higher
in test..
whereas as reference formulation is absorbed faster,
the fe could be higher (more drug escapes from first
pass) so less drug is metabolized from reference.
But again…why a HS-HP is having different absorption
rate from different formulations???...
Both formulations should release the drug in less than
30 mins..so the concentration profile along all GI
should be the same..so…I have no reasons for expecting
differences in magnitude or in rate…Unless you are
having a real problem with your formulation.
Any excipients affecting GI motility?
Sorry for the long mail...
Marival
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)