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The following message was posted to: PharmPK
In 2001, the following paper was published:
Diehl, K-H et al., (2001). A Good Practice Guide to the Administration
of Substances and Removal of Blood, Including Routes and Volumes. J.
Appl. Toxicol. 21: 15-23.
Since that time, I and other Study Directors at two CROs of which I am
aware, have, with IACUC approval, been using the limit permitted by that
paper, of 20% of total circulating blood volume of laboratory animals
for pharmacokinetic or toxicokinetic blood sampling over 24 hours.
(I am aware that a number of institutions have not adopted this upper
limit and enforce a lower maximum of 15% or even only 10%. This email
is NOT intended to start a thread about whether any IACUC is "right" or
I know of at least three IACUCs, and a substantial number of laboratory
animal veterinarians who have been satisfied that the 20% upper limit
does not have discernable negative impact on the wellbeing of the
animals. However the question remains whether removal of 20% of blood
volume by increments over 24 hours has any effect on toxicokinetic
parameters. Therefore my question relates not to an animal welfare
issue but to the scientific advisability. Although it seems reasonable
to suppose that the animal would rapidly adapt to reduced circulating
volume, when the volume is removed stepwise, it seems to me that the TK
or PK parameters could be affected, for example if the test article in
question is highly protein-bound and the serum proteins are being
In my own experience, I have not seen any evidence of any effect on TK
parameters with 20% removal over 24 hours, even when conducting studies
with monkeys ranging in size from 1.5 kg to 4 kg bodyweight (with the
20% calculated for the smallest monkey on study).
This email is to ask whether anyone else who is using the 20% upper
limit has ever seen an effect on TK or PK parameters?
For that matter, has anyone seen an effect on TK or PK parameters as a
result of removing 15% over 24 hours?
Rosalind Dalefield, B.V.Sc., Ph.D., D.A.B.T
505 King Avenue
Columbus, OH 43201-2693
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20% blood removal over 24 hours doesnt qualify to be a hypovolemic
condition which may have a significant effect on PK/TK parameters. So
you may not see major changes in these properties.
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