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The following message was posted to: PharmPK
Dear Members,
We have carried out PK of a compound following PO & IV
administration in rats and mice. Second humps/peaks
were observed at about 6 – 8 h in case of oral
profiles but not in IV profiles in both species.
Could this be due to enterohepatic recirculation. Is
it possible to see a second hump in oral data but not
in IV data even if the compound undergoes EHR.
The pKa's of the compound are about 6 and 8. Its
solubility is low at pH < 7.4 and high at pH >10.5.
Moreover, no major metabolites were detected in the
bile until 8 h and its glucuronide in bile was <5%.
Based on this information could we say that the second
humps are due to precipitation and/or absorption from
two sites in the GIT rather than EHR (similar to
saquinavir). Any suggestions would be highly
appreciated.
Thanks in advance.
Regards,
Sreeraj Macha
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Comment:
Look into possibility of delayed gastric emptying....
Sureb
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It is for sure that you donot have EHR, however sometimes double peaks
happen as a result of improper formulations (PO) releasing the drug in
stages.
Ahmad
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