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The following message was posted to: PharmPK
Hi and hello,
I am currently working on pharmacokinetic
study of a semisynthetic compound that exhibit a
non-consistent( ie sometimes its biphasic and
sometimes its not) concentration versus time profile.
Any idea why this happens? I am using mice and ip as a
route of administration. Can anyone enlighten me about
the right way of doing a pharmacokinetic study. Your
opinions are well appreciated. Thank you
Thanks and regards.
From
Sandra
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HI Sandra,
Your drug may be rapidly distributing and showing biphasic
distribution. In this case sampling (time and the variability in
picking up samples) may otherwise result in marked variability in
profiles.
Also ensure that drug is not presititating (forming a depot) in the
peritoneum on ip injection.
Regards
Varma Manthena
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A few questions for you first. Are the monophasic profiles you are
seeing are more similar to the alpha or beta phase of the biphasic
profiles (or different altogether)? Is the phenomenon dose-related?
Is the phenomenon injection volume-related?
This information would be helpful in understanding your data. That
notwithstanding, there are numerous possible explanations for what
you are seeing with the following being a few of the more probable.
- The alpha phase and absorption slope coefficients may be close in
magnitude. Therefore with some variability in each of these
parameters, you are occasionally able to resolve the alpha phase.
- Drug could precipitate in the peritoneum thereby creating a depot
injection (i.e., beta phase reflects dissolution and absorption of drug)
- The lower limit of assay quantitation is truncating the beta phase
from the curves at lower doses
- You are not collecting data points at the appropriate times (either
early or late in the profile) to see the full shape of the curve
Regards, Jeff
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The following message was posted to: PharmPK
Dear Sandra:
Please provide more details as how do you construct
your PK profiles; are these single animal profile or N
of 3-4 animals per time points? In how many occasions
you have seen this? Did the same person perform all
the injections? Have you perform a crash test on your
formulation to at least have some idea of its tendency
to precipitate upon injection? I also perform iv
injection and get the profile; this is a more accurate
representative of your compound disposition profile.
Rostam
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