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I am looking some plausible reasons for :
Oral AUC's of a prodrug are significantly higher as compared to
the I.V AUC's of the same compound given in the native form.
e.g Compound X - Given as suspension orally yields AUC of 10,
injected I.V gives an AUC of 20 - F% (50).
Prodrug is made of the same compound and now the oral AUC's are
40???
Some comments/suggestions would be welcome.
Sandeep
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Are you adjusting for molecular weight in your calculations?. Compare
doses
and concentrations on equimolar basis if you haven't already done that.
Clapton Dias, Ph.D.
Pharmacokineticist II,
Global Product Development Services,
PRA International
16400 College Boulevard,
Lenexa, Kansas-66219.
Ph: 913-227-7257
Fax:913-599-2753
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Dear Sandeep,
I find the information you provide insufficient to be able to comment
on the issue. Your answers to a couple of simple questions might help.
Does your analytical system measure X directly? What is the difference
(chemical moiety) between X and its prodrug? And what are the molar
doses of X and its prodrug being administered (both the IV and the PO
experiments)?
Toufigh Gordi
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Did you compare the elimination half-lives of prodrug and the active
moiety?
Also knowledge of the rate and extent of conversion of the prodrug to
the
active molecule in vivo might help.
Ramesh
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