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Dear PK scientists
We are working on a compound which seems to have a 2 compartmental
elimination phase. This compound is converted into active metabolites.
Our preliminary results show a non-linear elimination pattern for the
parent compound. I suspect an enzyme induction process.
I have a functional model in winnonlin based on differential equations.
I have a good fit but a poor estimate of parameters. The estimation is
based on data obtained from plasma collection.I would like to
incorporate nonlinearity ( the effect of induction) into these
equations in my model to improve the estimation of the parameters. I
would appreciate if any of you fellow PK scientists could share your
experience with me in this regards. Ideally, I would like to see an
example of a non-linear model which is not clearance based.
Many thanks,
Delara Karkan
Senior PK scientist
Anapharm, (SFBC)
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The following message was posted to: PharmPK
Hello Delara
This reference might be of use.
Characterisation of the human liver in vitro metabolic pattern of
artemisinin and auto-induction in the rat by use of nonlinear mixed
effects
modelling.
Svensson US, Maki-Jouppila M, Hoffmann KJ, Ashton M.
Biopharm Drug Dispos 2003 Mar;24(2):71-85
Venkatesh Atul Bhattaram
CDER, FDA.
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The following message was posted to: PharmPK
Delara Karkan writes:
I would like to see an example of a non-linear model which is not
clearance based.
A nonlinear model that is not clearance related is paclitaxel, where
transfer to the peripheral compartment is saturable. See
http://dmd.aspetjournals.org/cgi/reprint/27/10/1220 for an example.
pete bonate
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)