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Dear All,
Sometime back there had been a discussion on the volume of blood that=20
can be taken from a rat for PK studies.
We are doing PK studies in rats and we serially bleed the rats in the=20
following fashion.
Group 1 : 5min, 30 min, 2 hr, 8hrs and 12 hrs.
Group 2: 15 min, 1hr, 4hr, 8 hrs and 12 hrs.
Our animal weight range is 140 - 160 g. At each time point we are=20
able to take a minimum of 1 - 1.2ml of the blood conveniently. During=20
the study rats have an free access to drinking water.
This design means we are taking almost 5.5 - 6 ml of the blood from a rat.
Will this design have an effect on any of the PK parameters like Cmax, or AU=
C.
Any comments would be appreciated.
M.Khan
LookSmart =85 or keep looking.
http://www.looksmart.com.au
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[Two replies - db]
X-Originating-IP: [203.197.255.53]
From: "NVSRAO MAMIDI"
To: PharmPK.-at-.boomer.org
Subject: Re: PharmPK Blood volume from rat
Date: Mon, 27 Dec 1999 23:19:25 PST
Dear Mr. Khan:
You cannot take that many samples with that sample size. This will
reflect your PK and lead to erroneous parameters.
The weight range you used is 140-160 gm, contains arround ~ 9.0 ml
of blood (based on the calculation-6.4% of body weight composed of
blood). So you are drawing 75% of the total blood volume over a
period of day.
Please go through the reference for more information
1. Biological effects of blood loss: implications for sampling
volumes and techniques, perspective on animal use, vol.31 No.4, 5-18,
1989.
N.V.S.Rao Mamidi M.Pharm., Ph.D
Senior Scientist,
Drug Metabolism and Pharmacokinetics
Dr.Reddy's Research Foundatin
Ameerpet
Hyderabad- 500 016
India
email: mamidi_nvsrao.aaa.hotmail.com
---
From: "danny_lee3"
To:,
"Multiple recipients of PharmPK - Sent by"
Subject: Re: PharmPK Blood volume from rat
Date: Mon, 27 Dec 1999 23:30:51 -0800
Organization: Microsoft Corporation
X-Priority: 3
PharmPK - Discussions about Pharmacokinetics
Pharmacodynamics and related topics
Mubeen:
The general rule used by most institutional animal care and utilization
committees (IACUC) is that no more blood than 10% of body weight can be
taken in a 24 hour period. Some committees may require you to replace with
equal volume of saline or preservative following each blood draw. We have
done this with jugular vein cannulations from which blood is drawn and
replaced with saline or a preservative to maintain catheter patency such as
sodium citrate or heparin. When clearing the catheter just before the blood
draw be sure to give back the animal's cells after the sample is taken. The
principle here is to not disturb hemostasis. If you are giving an IV bolus
drug you can do a dual cannulation of jugular and femoral vein. These
cannulas are run through a path cleared by a probe under the skin and both
exteriorized at the back of the neck. Makes one neat and easy place to dose
and sample and the animal can't get at it. It does not take too much
training for an animal surgeon to become proficient with this technique, if
allowed at your institution.
If you are sampling by serial tail vein sticks, good luck hitting the
tail-vein each time and not trashing the vein!
Ten percent of your animal weight range is from 14 to 16 mL of blood and you
are taking ~6 mL which is under 5% of body weight and should be perfectly
aceptable.
In considering this loss of blood volume or dilution by saline replacement,
the loss of plasma albumin may have an affect on protein-binding depending
upon the extent of binding. However, I would think that any effect on Cmax
and AUC will be minimal in your proposed sampling scheme.
Dan Combs
dzc.at.gene.com
Genentech, Inc.
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Sorry, my mistake! Dr. Mamidi is correct. You cannot take 75% of the rat's
blood volume. You could take ~10% of blood volume in 24 hours (not 10% of body
weight). Thus, you could collect 0.9 mL over your proposed 5 samples or 180
microliters per sample.
===========
Dan Combs
PK&Metabolism Dept.
Genentech Inc.
voice (650) 225-5847
fax (650) 225-6452
e-mail dzc.-at-.gene.com
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