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Dear all,
I have to build a physiological model of absorption, disposition and effect
in whole animal organ (rat or rabbit). Drug concentration will be measured
in tissue at various times in nerve, and blood flow will be measured in the
surrounding tissue at the same times; all measurements are done with a
spatial resolution leading to about three-five voxels. The goal is to
correlate PK and PD parameter with covariates.
I have the choice between two approaches: 1) use a complicated model with
diffusion and transfer between compartments, like models of liver
elimination, and 2) to use a more simple PK-PD model pwith analytical
solution and
incorporate covariates with a more sophisticated approach than with the
first model.
Personally I favor the simple model because of the principle of parsimony,
the fact that necessary assumptions are highly speculative in the first
(diffusion) model, etc...
What is your opinion and why.
Thank you in advance.
Jean Xavier Mazoit MD, PhD
Laboratoire d'Anesth=E9sie
Universit=E9 Paris-Sud
Facult=E9 de M=E9decine du Kremlin-Bic=EAtre
F-94276 Bic=EAtre France
Tel. (33) (0)1 49 59 67 35-37
(33) (0)1 45 21 34 41 (Hopital)
Fax (33) (0)1 45 21 28 75
e-mail Jean-Xavier.Mazoit.-at-.kb.u-psud.fr
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Dr. Xavier,
I would suggest that you use a simple model. The key to
building a working
model is to carefully choose the model:
1. data parameters
2. predictive capabilities
It is always easiest to work backwards from known---but not necessarily
understandable---results and attempt to measure data that can be expected
to predict those results.
Keep the mathematics simple and focus on identifying
measurable parameters
that you can back trace to groups of simple data sets.
I hope I have been clear.
With my most sincere wish for your success in a very difficult task,
D.B. Gross
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Jean-Xavier,
I'd use a semi-physiological model: classical PK model for the
plasma/blood input; physiological model for the part of the body in
which PD is relevant
Ce site est peut-etre utile:
http://www.simulations-plus.com/mnframe.htm
Christine
Experimental Medicine, GlaxoWellcome S.p.A.
Via Fleming 4, 37135 Verona, Italy
Tel. +39 045 921 9122 / Fax +39 045 921 8191
Office nb. 5040, GW Research building (5th floor)
Email: cf18544.-a-.GlaxoWellcome.co.uk
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