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Dear Sir
We would like to do a PK analysis of a drug following IV dministration
into rats. The blood volume sampled was 2.8 ml (collected at 0, 10, 20,
30, 40, 60, 90 min and 2, 3, 4, 6, 8, 10, 24 hr after the intravenous
administration, 0.2ml each time). This corresponds to perhaps 15-20% of
the animal's total blood volume, which is on the high side of what may
be considered acceptable? Could the blood loss affect the pk results?
Best wishes
sincerely yours
TX Qian
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Dear Qian,
You had mentioned that you had collected 2.8ml blood (15 - 20
% of the blood volume). I think it is within the acceptable range and
it does
not affect the PK results. If you are going beyond 20%, then you are
favouring the elimination of your drug by removing the blood, Where the
PK
results will be affected. Hope this will help you.
Regards
Fakrudeen-Amol
Wockhardt Research Centre
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Dear Qian
I think upto 15-20 % of blood collection would not affect PK study. You
have not mentioned the route of blood collection? If you are collecting
blood via jugular vein by doing canulation, you can always replace the
volume loss.
regards
Amol Raje
Wockhardt Research Centre, Aurangabad
India.
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I always thought that 10% of the total blood volume was a safer range
to aim at when doing PCKN studies in rats. Is it too conservative
then??
Alessandra
Alessandra Milesi-Hall=E9
Department of Pharmacology and Toxicology
University of Arkansas for Medical Sciences
4301 West Markham, slot 611
Little Rock, Arkansas 72205
Phone: (501)686-6551
Fax: (501)686-5521
MilesihalleAlessandr.at.uams.edu
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Here is what our IACUC veterinary told me: "Blood collection should be
limited to 1% total body weight within a 2 week period. A 300 gram rat
should be limited to 3.0 ml over this time period. Collection volume
can be increased to 2% body weight during this period if fluid
replacement is given, especially during the first 24 hours of
collection." I don't think he knows a lot about PK study, but he knows
rat physiology. A good PK study should be done in a healthy rat.
Jun
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Dear Quian,
yes, you can replace the fluid, but you are still left with the
possibility
that the amount of drug removed during blood sampling may be
substantial and
could influence the accuracy of estimation of pharmacokinetic
parameters.
One way around this problem is to include the drug lost by sampling
(especially the time profile of this drug loss) in your pharmacokinetic
model. WinSAAM has tools that facilitate this approach.
Details about WinSAAM can be found at WWW.WinSAAM.com
Regards,
Peter Moate
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Dear Qian,
I hope this article will help you.
Diehl et al (2001) A good practice guide to the administraion of
substances
and removal of blood including routes and volumes. J. Applied Toxicology
Vol. 21 Page no. 15-23.
Regards
Amol Raje / Fakrudeen
Wockhardt Research Centre, Aurangabad
India.
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