Back to the Top
Dear All, I would like to determine the clearance time of a drug
following I.V administration in Rats. In Bioanalytical analysis, the
drug content is determined in plasma obtained from blood samples.
Following processing of the blood samples by centrifugation to obtain
plasma, can I assume that all the drug in the blood has passed into
the plasma. What is the expected recovery? For example if after a
certain time point no drug is detected in the plasma samples
(analyzed by a validated method) can I assume that no drug is present
also in the blood circulation ?. Thanks in Advance, Leo
[You should expect drug in the red blood cells when there is drug
measured in plasma - db]
Back to the Top
The following message was posted to: PharmPK
Dear Leo,
There are examples of drugs distributing to RBCs preferentially.
Hydrochlorothiazde is one I am familiar with. In general, one assumes
that there is no circulating drug if none detected in plasma, but
some may be present in RBCs. Depending on the goals of your study,
you could measure drug in whole blood and plasma or RBCs and plasma.
This way you will cover the blood compartment. There was a good
article on this topic that I came across a couple of years back.
Maybe members of the list will have reference for you.
Katya Tsaioun, Ph.D.
President
APREDICA
313 Pleasant Street, 1st Floor,
Watertown, MA 02472
Back to the Top
The following message was posted to: PharmPK
Leo,
You cannot assume centrifugation will move drug from the RBCs to the
plasma. You really need to determine the plasma to blood ratio.
For many of the compounds I work with, the plasma protein binding is
>98%. So for all intents and purposes, all of the compound is
associated
with plasma. For drugs with higher free fractions, this may not be the
case.
Susan Shoaf
Otsuka Pharmaceutical Development & Commercialization, Inc.
Back to the Top
The following message was posted to: PharmPK
Dear Leo,
> For example if after a certain time point no drug is detected in
the plasma
> samples(analyzed by a validated method) can I assume that no drug is
> present also in the blood circulation?
It all depends on the relative affinity of the drug in question to RBCs
vs. plasma proteins. Even the drugs with high protein binding can
partition into RBCs if the affinity to RBC components is greater over
that of plasma proteins. So, it is important to determine
blood-to-plasma partitioning ratio to understand relative affinity. For
drugs with blood-to-plasma ratio equal to or less than 1, it is
reasonable to assume that no drug is present in the blood if it is not
detected in the plasma. On the other hand, for drugs with
blood-to-plasma ratio greater than 1, it is possible that drug may be
present in the blood even if no drug is detected in plasma and higher
the blood-to-plasma ratio greater the chances for that to be the case.
Hope this helps.
Kasiram.
Back to the Top
The following message was posted to: PharmPK
Best to say the drug was below the limit of detection, and leave it
at that.
Ed O'Connor, Ph.D.
Laboratory Director
Matrix BioAnalytical Laboratories
25 Science Park at Yale
New Haven, CT 06511
Phone: 203.789.1800
Web: www.matrixbioanalytical.com
Email: eoconnor.aaa.matrixbioanalytical.com
|
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Correlation between drug in plasma and blood" as the subject | Support PharmPK by using the |
Copyright 1995-2011 David W. A. Bourne (david@boomer.org)