PharmPK Discussion - Ester metabolism

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On 18 Nov 2004 at 08:56:55, Nikhil Shetty (shetty_123123.aaa.yahoo.co.in) sent the message


Dear All,
I wish to know how to determine the site of cleavability of an ester
prodrug.
Incubations with serum, liver and intestinal S9 fractions can of course
give us an idea. But in some of our studies we have observed that ester
prodrugs are cleaved with the intestinal S9, however, still they
achieve higher AUC's as compared to the parent drug. How could I
explain this.
Any suggetions would be helpful.
Nikhil

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On 19 Nov 2004 at 06:12:04, manish issar (issarmanish.aaa.yahoo.com) sent the message


Nikhil
what kind of drug are you working on. is it a weak base or acid?
depends where and how it gets absorbed. if the drug is absorbed more
from the stomach and you checked the metabolism in the intestine then
that could be a reason. i am just guessing the possibilities. if you
give more insight then one can think more about it.
manish

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On 23 Nov 2004 at 09:09:21, Scharn.at.jerini.de sent the message


Hi Nikhil,
what do you mean with "higher AUC's", does the higher AUC correspond to
a
higher concentration ?,
or is your "ion-yield" from the ester just higher to to method-set-up
(pos.
ESI, unpolar compounds ...)?
best regards
Dirk
Dr. Dirk Scharn
Scientist, DMPK
Jerini Pharmaceuticals
Jerini AG
Invalidenstra=DFe 130
10115 Berlin, Germany
Phone:    +49-30-9 78 93-369
Fax:         +49-30-9 78 93-105
eMail:       scharn.-at-.jerini.de

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