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The following message was posted to: PharmPK
Hi to everyone,
I have some questions related to WinNonLin and physiological
pharmacokinetic models.
We have some animal datas (concentration vs time of brain, liver
kidney, spleen and blood) and we want to perform a test with phys-
pharm modeling with the hope to get "more" information out of such
an experiment.
Can anyone provide ascii models for WinNonLin ? Anyone ever
used WinNonLin for such a purpose ? Any ideas for other easy to
use software packages (because i do not want to write computer
software but compute my data!) ? Is there any good information
side on the internet ?
Thanxs a lot in advance !
Yours Daniel
Dipl.-Chem.
Daniel Eikel
Tierärztliche Hochschule Hannover
ZA 44 Lebensmitteltoxikologie
Zentrum für systemische Neurowissenschaften Hannover
Bischofsholer Damm 15 - Gebäude 123
30173 Hannover
Tel: 0049-(0)511-856-7780
Fax: 0049-(0)511-856-7680
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The following message was posted to: PharmPK
I would not attempt using WinNonlin for PBPK modeling. You are much
better off investing the money in SAAM II or even WinSAAM. If money is
no object you might look at ACSL Tox which was designed for building
such models.
Good luck,
Pete Bonate
Peter L. Bonate, PhD, FCP
Director, Pharmacokinetics
ILEX Oncology, Inc
4545 Horizon Hill Blvd
San Antonio, TX 78229
phone: 210-949-8662
fax: 210-949-8219
email: pbonate.-at-.ilexonc.com
[Does WinNonlin now include numerical integration routines for stiff
systems? If not, that would limit its usefulness with PBPK models.
ADAPT II could work if you have access to a FORTRAN compiler but it
would involve some programming. Boomer can do some basic PKPB modeling
- db]
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The following message was posted to: PharmPK
Hello:
I have used WinNonLin to do some PBPK modeling. It can be done, but not
convenient and straight forward. There are some software designed for
PBPK
modeling that is easier to use, and easier to modify the model. As
Peter
Bonate mentioned in his email that ACSL Tox is one of them. There are
predefined basic blocks for building a PBPK model in ACSL Tox. Those
blocks
are designed based on three different mass transfer phenomina: flow
limited,
membrane limited, and neither flow nor membrane liminted. As I know,
Aegistg,
the company currently own the software is continue working on the
product to
enhance the program. Go to Aegistg.com you can find more information.
xiaofeng
Bristol-Myers Squibb
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The following message was posted to: PharmPK
Daniel:
A model is what the name indicates: a representation of reality, based
on certain assumptions. It is not reality itself. Hence, use of models
needs to be tempered with an understanding of the validity of the
assumptions that are being used. Above all it is necessary to determine
the model(s) chosen is (are) valid for the particular study, and
whether they answer the questions being asked.
Having an equation and putting numbers into an equation will give you
some results. For such results to have any meaning - e.g., to give you
more information, as you ask, you need to analyze what you are doing
and determine whether the model(s) chosen are appropriate to answer
your questions.
A good physiological model is one that aims to estimate true
physiological parameters - e.g., influx and eflux from a given tissue
or organ, rate of metabolism of a given compound, etc. One of the
problems you have when you use pooled animal data is that you are
averaging various individuals, each of whom may have subtle but
meaningful changes in specific parameters. Noninvasive imaging allows
you to measure changes in a single individual, but that is only
possible if you are able to measure the drug/metabolites you are
interested and if you have the equipment to do so.
Start by defining the question(s) you are trying to answer. Then you
can determine what models may be able to answer your question(s), and
only then will you be able to select the techniques that provide the
necessary input data for these models.
Professor Walter Wolf, Ph.D. President, Correlative Imaging Council,
Society of Nuclear Medicine
Distinguished Professor of Pharmaceutical Sciences
Director, Pharmacokinetic Imaging Program
Department of Pharmaceutical Sciences, School of Pharmacy
University of Southern California 1985 Zonal Ave., Los Angeles, CA
90089-9121
E-Mail: wwolfw.-a-.usc.edu
Telephone: 323-442-1405
Fax: 323-442-9804
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The following message was posted to: PharmPK
To Daniel and others wishing to do physiological /pharmakokinetic
modeling,
this type of problem can easily be modeled using WinSAAM. A paper
describing the modeling capabilities of WinSAAM was recently published:
Stefanovski D, Moate PJ, Boston RC: WinSAAM: A windows-based
compartmental
modeling system. Metabolism. 52:1153-1166, 2003.
Information about WinSAAM can be found on the WinSAAM website:
www.WinSAAM.com.
In addition, a "hands-on" workshop conducted by Dr. Ray Boston (the
developer of WinSAAM) will be held at Kennett Square (30 km west of
Philladelphia, PA)on 29th and 30th of January 2004. The cost of the 2
day
workshop is only $1090.00. For this price you get to attend the
workshop,
recieve a CD with the latest version of WinSAAM and a textbook on
compartmental modeling. Information about the workshop can be found at
www.WinSAAM.com. Note that WinSAAM now contains a population modeling
tool.
Places in the workshop are filling up fast. Those wishing to obtain a
program of the workshop or to register for the workshop should contact
Peter
Moate. Email: moate.at.vet.upenn.edu Phone:6109256146
Regards,
Peter Moate
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The following message was posted to: PharmPK
You can also check SAAM II (www.saam.com) which is a multicompartmental
application used in biological and pharmacological kinetics. It is very
convenient to use being fully menu driven with a transparent graphical
user
interface.
David Foster, CEO
SAAM Institute, Inc.
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Or you might consider GastroPlus - a PBPK module is in early testing
right now, and will be released early in 2004. This will provide a
fully coupled PBPK module with the world's most accurate and most
widely used oral absorption/pharmacokinetics/pharmacodynamics
simulation software.
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (SIMU)
1220 W. Avenue J
Lancaster, CA 93534-2902
U.S.A.
http://www.simulations-plus.com
Phone: (661) 723-7723
FAX: (661) 723-5524
E-mail: walt.-at-.simulations-plus.com
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The following message was posted to: PharmPK
Daniel,
there are many solutions around which can be used to setup and solve
physiological PK-models (as you see from the many answers to your
question).
However writing the code and solving the differential equations is not
the
problem at all. That can for not so sophisticated models in principle
be done
with a simple spread sheet. The main hurdle is the parameterization of
the
equations for which you need information as e.g. steady state organ to
plasma
partition coefficients and permeability surface-area products for the
permeation
into the organs.
To my knowledge the only software including a ready to use universal
whole body
PBPK-model which allows PBPK-modeling without worrying about model
development
and that does the parameterization by itself on the basis of a handful
of easily
obtainable compound specific data is PK-Sim (see http://www.pk-sim.com).
Best Regards
Walter Schmitt
Bayer Technology Services GmbH
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Dear Daniel,
As the others have stated, I personally would not try to use WinNonlin,
although it could be done if a user defined model were to be written.
It would have to be compiled to a DLL to make it run fast enough to be
useful.
In Novartis we use ACSL (as ACSL-Tox, or the old Dow-Corning SimuSolv
on a VAX), MatLab, SAAM II, ADAPT II and the Berkeley Madonna to create
such models. I have also written models in NONMEM although not used
them to do anything other than simulation so far (with parameters
estimated from one of the other softwares). However, NONMEM is useful
for running Monte-Carlo simulations of PBPK models to generate
prediction intervals, which it can do rather quickly (<5 min for N=1000
of a 30 compartment model with non-linear blood cell binding).
Best regards, Phil.
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Dear all:
About WinNonlin or Saam, you might also consider the USC*PACK
collection for population modeling. The methods are consistent, and
statistically efficient compared to many other methods. Information is
on our web sitewww.lapk.org.
Very best regards,
Roger Jelliffe
Roger W. Jelliffe, M.D. Professor of Medicine,
Division of Geriatric Medicine,
Laboratory of Applied Pharmacokinetics,
USC Keck School of Medicine
2250 Alcazar St, Los Angeles CA 90033, USA
Phone (323)442-1300, fax (323)442-1302, email= jelliffe.at.usc.edu
Our web site= http://www.lapk.org
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The following message was posted to: PharmPK
Hi Daniel,
for the set-up of physiological PK models we use the program ModelMaker
(see www.modelkinetix.com).
The graphical interface is easy to use, and the program works well,
especially for not-too-complex models.
ACSL requires, but also allows more "programming", and is therefore
suitable for more sophisticated approaches.
(We use WinNonLin here as well, but not for PBPK modeling.) Besides,
ModelMaker is not expensive to aquire.
I hope this helps you to chose a suitable program.
Hi all,
who else is using ModelMaker for PBPK Modeling?
It would be great to exchange ideas!
I am looking forward to your answers.
Best regards
Christian
Dr. Christian Lüpfert
Schering AG, Berlin
Research Pharmacokinetics
Tel.: +49 - 30 - 468 - 16723
Fax: +49 - 30 - 468 - 12238
Christian.Luepfert.at.Schering.de
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)