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Dear All,
As explained in the publication J Pharmacokinet Pharmacodyn 2007; 34:
57-85, the major reason to use the rate of delivery is to estimate the
parameter EDK50 which is the product of the clearance and the EC50. It
gives an easy estimation of the dose that could be given at steady-state
which is the EDK50 multiplied by the dosing interval. The covariates
that influence the clearance and the EC50 (usually the PK-PD parameters
we are most interested in) will also influence EDK50. EDK50 is not
influenced by the volume of distribution. The approach that uses the
concentration estimates an ED50 that depends on the volume of
distribution and its covariates. From a PK-PD and covariate analysis
point of view, I found this later approach less attractive. We all agree
that the concentration drives the effect, but parameterization gives
some advantages that can serve our goal.
Best regards
Philippe
Philippe Jacqmin, PhD
Life Science Services - Exprimo
Director
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The following message was posted to: PharmPK
Philippe,
Why not use a PBPK model and get a better understanding of what it going
on? Simplified models can mask a variety of interacting mechanisms that
require reparameterizing the model whenever something is changed. A single
mechanistic model that explains all your data provides valuable insight
and can save a lot of "chasing your tail" - which is expensive.
Best regards,
Walt
Walt Woltosz
Chairman and CEO
Simulations Plus, Inc. (NASDAQ: SLP)
42505 10th Street West
Lancaster, CA 93534
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