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To the members of the pharmPK discussion group
I am seeking for a computer program which is able to fit
concentration-effect curves of several experiments with the same drug
(e.g. n=6) and to determine an Ec50 +/- s.e.m., slope and maximum and
to compare it with a different experiment (different drug or presence
of an antagonist; e.g. also n=6) and to determine whether the
parameters are significantly different or not. Until now, we use a
program modified from a program of Waud which works with a logistic
function
e = (K1*A^K2)/(A^K2 + K3^k2)
where
e: Effekt
A: Concentration
K1: maximum value
K2: slope
K3: EC50
However, the determined s.e.m. is very small, probably because it is
determined only by the deviation of all single points from the curve
which is fitted through these points. My suggestion would be that
each individual experiment should reveal an individual
concentration-effect curve (with some error regarding the deviation
of the points from the curve) and then the Ec50 and the other
parameters (for n=6) with s.e.m. shold be computed.
I would be very happy if someone could help me
Sincerely
Wolfgang Vierling
Institute for Pharmcology
Technical University Munich
Tel. 0049-89-4140-3282
Fax 0049-89-4140-3305
Dr. Wolfgang Vierling
Institute for Pharmacology
Technical University Munich
Biedersteiner Str. 29
D-80802 Munich
phone.: 0049-89-4140-3282
fax.: 0049-89-4140-3305
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We use SigmaPlot by Jandel Software it has a good curve fitting module
that provides a standard error.
Curt Mazur
IDUN Pharmaceuticals, Inc.
cmazur.at.idun.com
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There are many programs which will do this but very few that will take
into account the differences between individuals. If the latter is
important to you then I would recommend NONMEM. Installation and
training in the use of this program will require some effort but once
you have mastered it you will find it has many applications in
pharmacological analysis.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, Private Bag 92019, Auckland, New Zealand
email:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.html
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You may be interested by the work of Davidian et al. :
Davidian M, Giltinan DM, 1993, Biometrics, 49, 59-73
Giltinan DM, Davidian M, 1994, Statistics in Medicine, 13, 1165-1179
They use a maximum likelihood method to fit each curve, and then an
EM-algorithm to estimate the distribution of the model parameters.
A Turbo Pascal program which implements a variant of this method
(applied to the more simple Michaelis-Menten equation, and without the
EM step) is available on my web page.
I hope this helps.
Sincerely
--
Jean Debord
Laboratoire de Pharmacologie, Faculte de Medecine
2 Rue du Docteur Marcland, 87025 Limoges (France)
http://ourworld.compuserve.com/homepages/JDebord
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)