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Dear all,
I would like to have your input to a question about the
implementation of a blood sampling method for PK studies in mice.
At the moment we are performing our PK studies in the way that we
dose two mice per timepoint. All blood samples are taken from heart
which means we use 1 mouse/sample, have to be aware of
interindividual variations within our studies, and we also use quite
a lot of mice per study.
We want to shift now to a method where we take one or two samples
from the sephanous vein per mouse before taking blood from heart from
the same mouse. This would give us a more intraindividual readout for
at least two or three timepoints and reduce the number of mice used
in the studies.
My question now is do I have to expect differences in PK parameters
between the different sampling methods in terms of Cmax, Tmax, T1/2,
elimination values, etc when I take blood from the vein compared to
the heart?
I have another more general question. What is a "normal" variation of
drug concentration in plasma samples taken from different mice at the
same timepoint and concentration (2-fold or rather 10-fold)?
Thx in advance
Matthias
--
Matthias Reule PhD
29 Hoadly Road
Cambridge
CB3 0HX
UK
matthias.reule.-at-.googlemail.com
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Matthias,
There are lot of different opinions about this issue. Many people
have shown no significant differences while others have shown
siginificant differences (due to differences in various hematological/
biochemical parameters) in PK parameters between different sampling
methods .
It may also depend on your drug substance and its pharmacological
effect on blood flow. So you may or may not see the differences in
one or more PK parameters.
About your second question, it is difficult to define the normal
variation in plasma concentartion from different mice at the same
timepoint. You may want to increase the number of mice in a group.
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