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Dear group,
We are setting up a portal catheterism model in the rat (administration and
sampling - PK/absorption and metabolism issues) and would like to implement
this one by adding a second catheter in the systemic flow. We hesitate
between the femoral artery and the femoral vein. What are the
advantages/drawbacks of these two possibilities ? Could any of you help us
in making the better choice ? It will be very nice of you too to provide me
with some good references on the subject.
Many thanks.
Pascal ESPIE
Product Safety and Metabolism department
UCB Pharma
Chemin du Foriest
B-1420 Braine-l'Alleud
Belgium
Tel : + 32 2 386 33 40
Fax : + 32 2 386 27 98
Mail : pascal.espie.-a-.ucb-group.com
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The following message was posted to: PharmPK
Dear Pascal,
Use femoral vein for IV drug administration and the femoral artery for blood
sampling. The reasons are very simple: it is easier to push the dose
solution into the vein but easier to draw the blood from the artery. Based
on my experience when I was a graduate student at Washington State
University, femoral vein is easier to cannulate for beginners while the
artery is much easier to handle after you have experience with say 10-20
rats' cannulation. The artery has also much less chance of getting clotted
over night (for repeated sampling purpose). Please see my paper with Dr.
Mohsen A. Hedaya as listed below.
Good Luck!
With Kind Regards,
Wei-Jian Pan, Ph.D.
Sr. Scientist
Clinical Pharmacokinetics (RD-2B)
Allergan, Inc.
2525 Dupont Drive
Irvine, CA 92612-1599
Phone: 714-246-4325
Fax: 714-246-6510
E-mail: pan_wei-jian.aaa.allergan.com
Pan, W. J. and Hedaya, M. A.: An animal model for simultaneous
pharmacokinetic /pharmacodynamic investigations: application to cocaine.
Journal of Pharmacological and Toxicological Methods 39:1-8, 1998.
Pan, W. J. and Hedaya, M. A.: Cocaine and alcohol interactions in the rat:
effect on cocaine pharmacokinetics and pharmacodynamics. Journal of
Pharmaceutical Sciences 88:4, 459-467, 1999.
Pan, W. J. and Hedaya, M. A.: Cocaine and alcohol interactions in the rat:
pharmacokinetic and pharmacodynamic contributions of cocaine metabolites.
Journal of Pharmaceutical Sciences 88:4, 468-476, 1999.
Pan, W. J. and Hedaya, M. A.: Cocaine and alcohol interactions in the rat:
effect of cocaine and alcohol pre-treatments on cocaine pharmacokinetics and
pharmacodynamics. Journal of Pharmaceutical Sciences 88:12, 1266-1274,
1999.
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[Two replies - db]
From: "Thomas A Torda"
Date: Tue, 11 Dec 2001 15:55:01 +1100
To: david.aaa.boomer.org
Subject: Re: PharmPK Re: Catheterism in the rat (portal and systemic)
Status: R
The following message was posted to: PharmPK
I don't know if this is relevant, but for the first 3-5 min (in humans)
there are significant concentration differences between peripheral venous,
central venous and arterial drug concentrations.
Tom Torda
---
From: bangarurk.-a-.drreddys.com
Date: Tue, 11 Dec 2001 18:27:15 +0530
To: david.-a-.boomer.org
Subject: Re: PharmPK Re: Catheterism in the rat (portal and systemic)
The following message was posted to: PharmPK
Dear Pascal,
I wanted to add that Jugular vein is very easy to cannulate and also for
blood sampling as well as I .V Drug administration. Even in rats of
100-150 gms, jugular vein cannulations are easy at least for graduate
students.
Ramakrishna Bangaru
M.Pharm .,( Ph.D)
Biopharmaceutics Research
Dr. Reddy's Laboratories, Generics
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I do not believe the problem of initial time-dependent concentration
differences in various vessels is of concern in the rat due to their small
size and very rapid circulation (~350-400+ beats/min). As Dr. Pan pointed
out, dosing is typically via the vein and sampling via the artery. This is
for practicality and ease. With this convention, even if both vessels are
cannulated in the same leg, there should not be any errors introduced in
determining accurate concentrations (because dosed drug must travel back to
the heart and through the system to reach the femoral artery for sampling).
But if for some reason, the reverse set-up is used (artery is dosed & vein is
used for sampling) and the cannulas are in the same leg, then I believe the
first very early sample may be artifactually high. (any input or comments
welcome).
One solution if there are any concerns is to cannulate the right femoral vein
for dosing and the left femoral artery for sampling.
Just an additional thought - if surgery's not your thing or you want to keep
it to a minimum - nonsurgical dosing can be via the lateral tail veins in the
rat (as long as excessive repeated dosing isn't necessary). For sampling,
retro-orbital bleeding (aka orbital sinus venipuncture) can be used with light
anesthesia.
P.S. I don't believe sampling from the artery vs. vein following portal vein
administration offers any inherent advantage.
Sincerely,
Dave Jaworowicz
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