- On 14 Aug 1997 at 13:47:54, "Wolfgang Vierling" (tbn02aa.at.sunmail.lrz-muenchen.de) sent the message

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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 - On 15 Aug 1997 at 10:35:30, Curt Mazur (MAZCU01.-a-.idun.com) sent the message

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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 - On 15 Aug 1997 at 10:36:50, Nick Holford (n.holford.aaa.auckland.ac.nz) sent the message

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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 - On 18 Aug 1997 at 15:49:29, Jean Debord (jdebord.at.MicroNet.fr) sent the message

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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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