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The following message was posted to: PharmPK
Hi all,
We have a compound that is given i.v. to the dog. After
a dose of 0.1 mg/kg AUC was 13250 ng-hr/mL and after
0.5 mg/kg AUC was 2863 ng-hr/mL. We have considered a
misdose, however we also saw the same trend following
oral dosing (3 mg/kg, AUC=5967 ng-hr/mL and 10 mg/kg,
AUC = 852 ng/hr/mL). These are the only studies we
have to work with at this time. They were conducted
at different sites, so I'm reluctant to think it was a
problem with dose prep.
Glucuronidation was observed in the plasma samples and
the compound has a half-life of about 10 min in dog
liver microsomes.
Any ideas as to what could be happening.
Thanks
Lynne
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The following message was posted to: PharmPK
Hi Lynne,
The information you provide is too little to be of much value. Several
questions arise:
- Were doses given to the same or different animals? If the same animals
received repeated dosings, how long apart were the doses given? What are
the enzymes that metabolize your compound? Do you have any indication
from animal studies that your compound induces enzyme activity?
-How good are you AUC estimations? What is the % extrapolated, i.e.
AUCt-inf over AUC0-inf? And what about the Cmax values? Do they show the
same trend?
As you might guess, my questions try to address the two hypothesis that
come to my mind: (auto)induction of metabolizing enzymes and poor
estimation of parameters. Maybe more information can help understanding
the cause of your strange observations.
Toufigh Gordi
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The following message was posted to: PharmPK
Dear Lynne,
You didn't do any work with rodents before you started on dogs???? Any
special resaon?
Kind regards,
Frederik Pruijn
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)