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The following message was posted to: PharmPK
Hi all,
I'm injecting a drug via the intrathecal route with an implanted
catheter. This device is then used to sample the CSF. 300 µl of CSF is
sampled for each time point (150 for the dead volume of the KT and 150
are kept for analysis). After analysis using LC/MSMS, I have the
profile of CSF drug concentration versus time. In log scale one can see
a distribution phase (rapid log linear decrease of the concentration in
the CSF, during the first 3 hours) after the decrease is slower and
linear. What PK parameters is it possible to calculate from this set of
data? I have performed a non compartmental analysis using kinetica. The
software calculate MRT and Thalf (I have chosen IV bolus model) is it
correct in that case?. The Vd given by the software is calculated from
the cmax, do I have to extrapolate a c0 from the elimination process
after initial distribution to calculate the apparent volume of
distribution in the intrathecal space? In parralel I have injected the
drug in plasma and calculated the PK parameters, but I don't know
precisely how to relate this parameters to the one I have calculated
for the intrathecal route.
if you have any litterature advice that i could use to solve this
problem please feel free to help me.
thanks very very much in advance to everyone who will take a few
minutes to help me.
Frederic lagarce
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Dear Frederic lagarce
Using data one can do many calculations, programming. Ultimately what
is important whether these serve to you objectives or not.
Please tell us about your project objectives
DrPrashant
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The following message was posted to: PharmPK
Dear Frederic,
The common parameter here is thalf, as this measures the terminal
systemic
half-life which should be the same following any dose method.
You haven't described the drug and objectives but I guess you are
interested
in localised acute concentrations of drug. Cmax and AUC in the
intrathecal
space and maybe some dynamic measurements such as Emax and EC50 would
be of
interest.
Vd is usually calculated from clearance and elimination rate and would
be
different initially but following distribution should be similar for
the two
routes (Vz = Cl/kel). Clearance comes from expression, Cl = Dose/AUC.
The
AUC should be determined from plasma.
Hope this helps.
William Heijbroek
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)