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The following message was posted to: PharmPK
Dear All,
If we want to estimate the levels present in CSF of humans on what
basis we have to select the time point.
Can we take a point basing on the Cmax achieved in the systemic
circulation ?
Ravi Kanth Bhamidipati
Senior Pharmacologist
Dept.of Drug Metabolism and Pharmacokinetics
Discovery Research Division
Dr.Reddy's Laboratories Ltd.
Bollaram Road , Miyapur
Hyderabad - 500 050
Andhra Pradesh
India
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The following message was posted to: PharmPK
Ravi,
This really really depends on the distribution characteristic of your
NCE.
Trimethoprim and Sulfadiazine both exhibit 2 compartment kinetics
following
IV admin.
I showed that trimethoprim CSF concentrations behaved as if CSF was
part of
the ideal second compartment. Therefore, TMP CSF concentrations could be
predicted by solving for plasma drug concentration in the second
compartment.
For SDZ, CSF concentrations mostly plateaued from 1.0 to 8 h post-dose
while
plasma concentrations fell. At 8-24 h, plasma and CSF fell with the same
half-life and CSF and plasma concentrations were not significantly
different.
Susan
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The following message was posted to: PharmPK
Dear Ravi
Since you are going to tap Human CSF I believe the patient would
have had a ventricular shunt already installed. In that case it
will not be a measure problem in collecting CSF at various time
points. If you have administerd the drug before then it is
necessary to do predose levels. Otherwise even if you collect a
sample at plasma Tmax it may not yeild the valuable information
available.
You do not have animal data? (not csf but at least brain
levels).
The Tmax in plasma and tissues can differ sometimes significantly
depending on the molecular properties (Structure and
Pharmacokinetics Correlation, n vivo conditions , etc.
with regards
Dr. Prashant
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)