Back to the Top
Dear Goup member,
Greetings!!!
Again here with a new situation, I carried out single dose oral PK
study in SD Rats (N=3 with serial sampling approach) for 72 hrs. at 20
mg/kg dose with a formulation consisting 10% tween 80 and rest 0.25%
CMC suspension.I got initial plasma levels below limit of quantitation
of my bioanalytical method and last 2-3 point were showing increasing
concentration.
So, later I planned another study for five days with similar
formulation and increaed the dose at 120 mg/kg. To my surprize, I got
similar conc. for 5 days without any decrease means elimination phase
is not at all there. The oral profile is just similar to sustained
release profile. In the mean time, I carried out SGF/SIF stability and
compound (NCE) was found to stable in both the conditions. So, pH
dependent degradation doesn't seem to happen and at the same time no
metabolism/ excretion (elimination) is not happening. There may be
some depot formation but no release (redistribution) is being taken
place upto five days????
I don't have any explaination for similar plasma levels of this NCE
for 5 days.
What you guys suggest me to do?????
Waiting to be enlightened on this issue....
--
Thanks and Best Regards,
Back to the Top
The following message was posted to: PharmPK
What is the stability/solubility at pH 1? At pH 8.0? What is the pH
solubility of your compound? What is the earliest time point? What are
the
points over the first 30 minutes? Are the animals eating and
defecating as
pre drug? A concretion in the stomach or intestine could occur-you
could
rule this out by checking fecal pellets/food intake or examining stomach
contents.
Back to the Top
wahajuddin,
Do you see the same profile in all rats? Whats the concentration range
achieved in plasma? Did your rats looked normal during the experiment
(is toxicity a concern?). I had seen this type of thing with one of
our compounds. It was highly toxic and virtually shuts down everything
in rat within 2 hr of dosing.
Also make sure that you dont deplete blood volume significantly in
serial sample (not more than 10-15% of total blood volume).
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Oral PK Profile of NCE similar to sustained release product for 5 day" as the subject | Support PharmPK by using the |
Copyright 1995-2011 David W. A. Bourne (david@boomer.org)