Back to the Top
Dear Colleagues,
What are the advantages (beside cost) and
disadvantages of using rats in mass-balance study for
PK (blood) sampling as well? Assume using cannulated
rat and total bleed volume of 1.5 mL (~10% of blood
volume, NO plasma or saline replacement, is it
critical to do this?) over 48 h or 120 h (6 bleed of
250 µL each). Is this approach acceptable by the
regulators (e.g., FDA)? I look forward to see some
good discussion on this.
Rostam
Back to the Top
You may want to review some physiology of volume depletion.
Back to the Top
Dear Rostam,
I have used this approach on several studies in the past, in the CRO
industry. The reason has always been based on client request to
minimize the cost of the study. To my knowledge, these clients did not
have any problems justifying the results to the FDA. With free access
to drinking water, IV fluid replacement should not be necessary under
the conditions you described.
Advantages:
1) Decrease in cost and time (which is billed back to the client).
2) Decrease in the number of animals used.
3) Decreases the amount of drug needed, especially if the drug is in
short supply or cost of production is very expensive.
Disadvantages:
1) Bleeding of the animals must take place in the metabolism cages.
This can be a challenge, depending on the type of cages that you have
available.
2) If you are planning on performing any metabolic profile analysis on
the plasma or excreta, consider the additional stress to the animals of
the cannulation surgery and the bleeding process. This increased stress
may have an affect on the metabolism and pharmacokinetics of the drug.
Good Luck,
Robert Sims
Senior Scientist, Drug Safety Evaluation
Midwest Research Institute
rsims.aaa.mriresearch.org
Back to the Top
If you look at the number of advantages and disadvantages listed,there
are more advantages than the disadvantages. The benefits are more than
the risks.Ignore the complains
Back to the Top
Dear commenter,
Are you aware of any specific issues/problems? Can you
share your example or case with the group? Any
references?
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)