Back to the Top
Dear everybody,
I am trying to learn more the indirect response models
and have a couple of questions. What does an Emax
really mean in such a model? Emax is used in the
variations of the model where the kin or kout is
increased. Does this Emax have the same meaning as a
Hill model, i.e. maximum effect? Or is it percentage
changes? The reason I ask is that in the other two
variants of the indirect response models, the maximum
value the Imax can get is 1, meaning a 100% (total)
decreae in kin or kout. If Imax is in %, so is Emax,
right? Or am I missing anything here?
I have looked at a couple of articles and the values
given for Emax do not seem to be either the maximum or
%change. It is very confusing.
Thank you for your kind help.
B Parta
Back to the Top
Batul,
The interpretation of Emax depends primarily on the form of the Emax
model. It has nothing to do with the the use of an indirect response or
a direct response model. The meaning of Emax will be the same for both
kinds of response model.
There are 2 variants of the Emax model:
1. E=Emax*C/(EC50+C) ; the standard Emax model
The interpretation of E (and Emax) is in the units of the response
being predicted e.g. mm Hg, if you were measuring blood pressure.
2. E=1-Imax*C/(IC50+C) ; the inhibitory Emax model
Imax and IC50 are exactly equivalent to Emax and EC50 but it often
convenient to use different symbols to indicate that this is referring
to an inhibitory effect of the drug.
The interpretation of E (and Imax) is a fractional change from a
nominal response of 1 in the absence of drug (C=0). Note this is NOT a
percentage -- it is a fraction of 1. Imax has a practical upper limit
of 1. If it is 1 then this means the response can be completely
inhibited by the drug. You may of course wish to multiply by 100 in
order to convert E and Imax to % of the nominal response in the absence
of drug.
Both variants can be extended to the sigmoid Emax form (i.e. 'Hill
model') without any change in the meaning of the parameters.
Nick
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
Back to the Top
Hello,
In the case of indirect response models, Smax/Imax represent maximum
fractional stimulation/inhibition of the bioflux, i.e, kin or kout from
its
basal value. They are unitless. Imax values range from 0 to 1 and Smax
is
any value greater than 0.
But in the normal Hill function model, Emax is the maximum effect and
has
units of effect.
Hope it is clear
Thanks
Mathangi
Back to the Top
For more info and discussion please check these messages:
http://www.boomer.org/pkin/PK00/PK2000111.html
http://www.boomer.org/pkin/PK01/PK2001138.html
Thanks,
Pravin
Pravin Jadhav
[Thank you for using the archive but these links may change in the
future. More likely with the current year references. It is better to
quote the search page (http://www.boomer.org/pkin/simple.html) and the
search terms used, thanks - db]
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)