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Dear all
I got a data from rat PK study following PO dose, it is very abnormal
and I hope to get your help to explain the data.
The drug concentration was around 700 ng/mL at 0.25 hr post-dose, and
it got Cmax 7000 ng/mL at 0.5 hr, then droped to 300 ng/mL at 1 hr. It
is very strange Cmax appeared so high and disappeared so quickly. I
have reviewed all of the procedures, dosing, bleeding, bioanalysis,
and no errors could be found. Did anyone obtain such data?
It would be great helpful if you could give me any possible
explaination. Thanks in advance!
Very best regards!
Yuming
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The following message was posted to: PharmPK
Errors can only be found if the data is recorded accurately. Retest
all the
dose formulations and initial bioanalytical samples-do not re-sample
diluted
samples. If nothing is apparent there, repeat the dosing(s).
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Dear Yuming
How many rats have shown the same profile? How about the samples after
1 hr. Was it solution dose? Fast / Fed?
Regards
Nabil
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what was the formulation? You can refer to following thread
http://www.boomer.org/pkin/PK04/PK2004405.html
(Oral dosing to rats)
Also check on plasma stability at 37C at different time points.
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Dear Nabil
We dosed two rats by PO after fasting overnight, they showed the same
profile. The dose formulation is solution, just 0.9% saline. The conc.
droped to 100 ng/mL at 2 hr post dose.
Now we will reassay the samples, hope to get some clues.
Many thanks and best regards!
Yuming
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The following message was posted to: PharmPK
Dear Yuming,
I would have the same questions as others on the forum :
what was the formulation dosed for PO dosing in rats?
did all rats give the same data?
Best regards,
Frederic DOC
fdoc.aaa.acriter-consulting.com
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Dear Yuming.
Did you find the metabolism, Vd, or elimination? that may help you to
find the reason.
Thanks
Dr Zafar
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Yuming,
I have a couple of questions...
what is the metabolic stability of the compound in the species for
which you have the oral exposure data and have you evaluated the
compound by IV administration?
If so what did the distribution phase look like, vd and half life?
What was the dose administered and is this a phenomena that is
repeated on dose escalation or reduction?
You can have very rapid absorption profiles with a rapid removal, but
we'd need more information...Interesting.
--
Sanjeev Thohan, PhD
SARx Consulting
SARxconsult.at.Gmail.com
http://www.linkedin.com/in/sanjeevthohan
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