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The following message was posted to: PharmPK
I am new to the world of pre-clinical studies and I would like to know
how I can determine which vessel is most appropriate to cannulate for
the PK studies I am performing. From what I've read, it seems common
practice to infuse through a femoral vein cannula and then perform blood
sampling through a jugular. Would it be acceptable to both infuse and
withdraw from the jugular? A CRO we worked with before did use only a
single jugular and if this is acceptable, it would be preferable for us
because we have someone who can do the surgeries in-house, but if we
have to double cannulate the rats, this individual will not have time to
perform all of the surgeries we would require. Thanks.
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From previous experience using cannulated rats, I do not think it is a
good idea to infuse drug and draw blood from the same cannula. That can
really screw up your drug concentrations in the blood expecially since
there will be a hint of compound left in the infusion cannula.
I believe getting double cannulated rats maybe the best way to get
blood samples from i.v. doses. I understand in house procedures are
more economical, but you want to make sure you are getting accurate
values from you plasma after infusing the drug.
Good luck
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The following message was posted to: PharmPK
I would think that the major concerns would be as follows:
(1) you would not be able to sample drug during the infusion of drug
without interrupting the infusion to allow withdrawal of the apprpriate
volume (deadspace of the tubing and the required sample volume).
(2) depending on the experimental design, there may be an error
introduced by sampling fromthe same site as the drug was administered
(i.e. not a well mixed sample)
(3) any sample after the completion of the drug administration would
still necessitate interruption of the basal infusion of fluid, etc.
In the end, the most rigourous study design may be the seperate
infusion site and sampling site.
Dhanesh
Dhanesh K. Gupta, M.D.
Assistant Professor
Division of Neuroanesthesia
Department of Anesthesiology
University of Utah SOM
30 N 1900 E Room 3C-444
TEL: (801) 581-6393 X313
PGR:(801) 249-1296
Salt Lake City, UT 84132
TEL: 801-581-6393
FAX: 801-581-6397
E-mail: Dhanesh.Gupta.-at-.hsc.utah.edu
E-mail: guptad.aaa.runbox.com
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The following message was posted to: PharmPK
I disagree with the two previous messages about this
subject:
From previous experience using cannulated rats, I do
not think it is a
good idea to infuse drug and draw blood from the same
cannula. That can
really screw up your drug concentrations in the blood
expecially since
there will be a hint of compound left in the infusion
cannula.
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Dear Rob,
Administering and sampling from the same cannula may not be such a good
idea: "Use of one cannula for both blood sampling and drug
administration: a potential cause of overestimation of drug
concentration. Kotegawa et al. Pharm. Pharmacol. Commun. 1998 4 283-5."
Alternatives to two cannulation sites are a double lumen cannula or to
put 2 cannulas in at the same site (jugular vein), which can be done.
Good luck,
Regards,
Bart
Bart Laurijssens
GlaxoSmithKline
CPK/MS Neurology
Greenford
United Kingdom
Telephone: +44 (0)20 8966 3814
Fax: +44 (0)20 8966 2123
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The following message was posted to: PharmPK
From my experience in CROs with IV infusion studies, I would suggest the
following:
For short infusion (bolus injection, or a single dose administered over
a
few minutes), you may not require surgical procedures as you can use the
tail vein while restraining the animals. For longer term infusion
(continuous infusion for hours, days, or weeks), the femoral vein is
usually preferred. The surgery is a bit easier to perform and the
catheter
tip will reach the aorta. Therefore, your volume of dilution will be
greater compared to the jugular vein (this may be important if the
compound
is irritant) and is farther away from the heart.
If you use a catheter, it is important to take the dead volume of the
catheter into consideration. There are two ways to do it but the
easiest
one is to fill the catheter with your compound before starting the
infusion. This way, the animals start receiving compound only when you
turn the pump on (time 0 of the infusion). When the period of infusion
is
completed, you turn the pump off. Make sure you do not flush the
catheter.
The other way is NOT to fill the catheter before the start of the
infusion.
In this case, you will have to calculate how long it takes for your
compound to reach the animal after the pump is turned on (based on the
rate
of infusion and the dead volume in your catheter). You will have to
flush
the catheter (with saline, for example) to complete the dose. It is
important to flush the catheter at the same rate you used for the
infusion.
For the same reasons given by other people earlier, the bleeding and
dosing
sites should be different.
GOOD LUCK !
Elen
elen lebel
morphochem AG
gmunder str. 37-37a
81379 muenchen
tel. ++49-89-78005-0
fax ++49-89-78005-555
elen.lebel.at.morphochem.de
http://www.morphochem.de
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In addition to previous comments, I would suggest dosing via a femoral
vein
but to do your sampling via a femoral artery, instead of using the
jugular
vein. Since one of your concerns is surgery time, you can perform both
cannulations in the same hind leg. You would not have to worry about
contamination of blood samples taken right after IV dosing since you're
using
two separate cannulas and the dose administered to the vein will travel
through the heart and back to the femoral artery before being sampled.
I
think this is the simplest and quickest surgical procedure which causes
the
least trauma to the animal.
Plus, using an artery for sampling will prevent problems such as plugged
(clotted) cannulas (especially at later time points) as well as
positional
cannulas which can result in difficulties in pulling samples at
designated PK
time points.
Always be sure to flush the cannula after each sample is taken.
Good luck,
Dave
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The following message was posted to: PharmPK
I agree with reply below. A study was conducted in humans with very
potent
opioid given IV. First early times 1-15 min or so came from arterial
line
with values in the pg/mL range. Then good rinse of IV port and
sampling then
continued from IV site. The poor GC/MS blew its mind over the very high
values (now many, many ng/mL) from residual drug in IV line.
Dave
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The following message was posted to: PharmPK
I disagree with the two previous messages about this
subject:
From previous experience using cannulated rats, I do
not think it is a
good idea to infuse drug and draw blood ...."
cannula.
From our previous experience you can use same cannula
if you take same basic precautions as flushing/washing
the cannula with saline after the infusion of the
drug. You can perform previously experiments with just
the cannula to check no detectable amounts of
compounds are adsorbed to the cannula. We have checked
that with our compounds and we have used use same
cannula flushing with saline after the infusion of the
drug. After taking a sample, we inject trought the
cannula again saline. Our Cp versus time curves are
not at all screwed up.
I agree with this concern:
(1) you would not be able to sample drug during the
infusion of drug without interrupting the infusion to
allow withdrawal of the apprpriate volume (deadspace
of the tubing and the required sample volume)
but not with this.
(2) depending on the experimental design, there may
be an error introduced by sampling fromthe same site
as the drugwas administered (i.e. not a well mixed
sample)
again this depends on you taking the precaution of
washing the cannula infusing a little additional
volume of saline. And the same procedure after the
withdrawal of a sample. You have to restore the blood
taken by saline.
(3) any sample after the completion of the drug
administration would still necessitate interruption of
the basal infusion
of fluid, etc.
We did not use any basal infusion of fluids as we
replace all the blood taken with saline and the animal
are conscious and with free access to water.
Marival Bermejo
http://www.uv.es/~mbermejo/absorption.htm
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The following message was posted to: PharmPK
Replacing removed blood with saline does not
maintain vascular volume. Saline is not restricted to the
vascular bed. Once pooled venous reserve is depleted, the
hematocrit starts to drop and functional circulating volume is
compromised. Sometimes you get lucky and this does not
adversely affect your PK studies. However, aggressive
sampling by this method can induce a shock-like syndrome
with compromised blood delivery to non-essential organs for
acute preservation of life.
Dan Sitar
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The following message was posted to: PharmPK
Hi Dan,
We have used donor rats for replacing blood with great success.
Taki
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