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The following message was posted to: PharmPK
Hi,
A drug I'm currently working with shows plasma clearances close to,
or above, the liver blood flow in different species. In line with the
recent discussion on a high clearance drug, I would like an
indication of whether this is due to a high liver extraction ratio,
and hence need an estimation of the blood to plasma ratio value.
Can anyone tell me of good methods to determine the blood to plasma
ratio experimentally?
Thanks in advance,
Regards,
Claus Larsen, M.Sc. (pharm)
Department of Early Development Pharmacokinetics
H. Lundbeck A/S, Copenhagen, Denmark
cll.-at-.lundbeck.com
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[Two replies - db]
From: Espie Pascal
Date: Fri, 14 Sep 2001 08:52:26 +0200
To: david.at.boomer.org
Subject: RE: PharmPK Determination of the blood to plasma ratio
The following message was posted to: PharmPK
Hi Claus,
Hope the following will help you ...
Freshly collected blood SD rat (fasted) withdrawn on citrate.
Distribution of 14C-compound between (i) erythrocytes and plasma and, (ii)
whole blood and plasma (theoretical blood concentration ca. 10, 100, 1000,
10000 ng/mL - add small volumes and check the influence of solvents).
After homogenization (0.5 h rotating at room temperature), an aliquot is
retained for determination of radioactivity in the blood and haematocrit is
measured. An aliquot is centrifuged (20 min.- 1000 g). Determine plasma
radioactive content.
After measurement of radioactivity in whole blood and plasma, the following
ratios are calculated ie. (i) erythrocyte/plasma distribution (C/B) and,
(ii) whole blood/plasma distribution (A/B).The concentration of
radioactivity in the erythrocytes C is calculated as follow :
[Embedded object deleted - db]
Where A, B and H refer to whole blood concentration, plasma concentration
and haematocrit, respectively.
Have a nice day,
Pascal ESPIE, PhD
Product Safety and Metabolism department
UCB Pharma
Belgium
Mail : pascal.espie.-at-.ucb-group.com
---
From: elke.stahl.es.-a-.bayer-ag.de
Date: Fri, 14 Sep 2001 10:36:08 +0100
To: david.at.boomer.org
Subject: Antwort: PharmPK Determination of the blood to plasma ratio
The following message was posted to: PharmPK
Hi,
- an blood to plasma ratio can easily be determined by spiking blood samples,
shaking them softly for e.g. 20 min, and analyze plasma concentrations. In
addition you need to know hematocrit of the sample.
- if it is due to hepatic extraction you can e.g. perform in vitro by liver
microsomal assays.
In addition, I would check for renal elimination and depending on the
Cl - first
of all on blood and plasma stability!
Elke Stahl
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