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I know of a drug company thinking of using concentrations to adapt
dosing in their drug development program. Does anyone know of Bayesian
forecasting software that might be customized for a specific drug with
2 compartment disposotion kinetics?
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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/
Dear Nick:Back to the Top
The USC*PACK software does this maximum aposteriori probability
(MAP) Bayesian task well. Also, our newer software that does "Multiple
Model" dosage design for maximally precise dosage regimens that hit
target goals with minimum weighted squared error from the target do
this even better. They use nonparametric pop models and do Bayesian
estimation of the individual patient's nonparametric posterior joint
density. In addition, they have the option of using the interacting
multiple model (IMM) approach for detecting changes in PK parameter
distributions DURING the period of data analysis, for patients who are
highly unstable and who have long dosage histories and more than a few
serum concentrations. They can catch the changing Vd and other
parameters in unstable patients receiving aminoglycosides, for example.
The new software thus can track changing parameter distributions in
unstable patients, and can always develop the mathematically most
precise dosage regimen based on the available info at the time.
You can get information about everything on our web site
www.lapk.org. Click around to new advances in pop modeling, and
teaching topics for more details about these approaches, and for demo
USC*PACK software, and info and costs. For the newer MM-USCPSCK
software, beta test versions are available at www.lapk.org/beta.
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.-a-.usc.edu
Our web site= http://www.lapk.org
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For Bayesian forecasting with a 2 compartment agent, I would strongly
recommend Roger Jelliffe's USC*PACK. I have used it extensively. I
would be interested in what their plan was for dosing within their drug
development program. Best regards,
Rob Ariano
Robert Ariano, Pharm.D.,BCPS
Clinical Pharmacist Critical Care
St.Boniface General Hospital; &
Associate Professor of Pharmacy,
& Medicine, University of Manitoba,
204-237-2050 Phone
204-237-2165 FAX
rariano.at.sbgh.mb.ca
www.sbgh.mb.ca
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Dear all,
As the major developer of MWPharm I can say that the software has
nothing to
do with the Abbott program but are own written routines based on simple
bayes algorithms and a simplex curve fitting. It can indeed easily
handle
some of the PK models. At this stage I can however say that it has been
outdated for a long time and has some major scientific problems and I
would
suggest looking at www.drudevo.com for some alternatives that uses an
easy
interface to NONMEM to do the same but a better job.
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Dear NM,
Would you please explain how an interface to NONMEM can help do a
better job of individual dose forecasting? I am familiar with using
NONMEM to solve the basic problem of producing MAP Bayesian PK
estimates. Does your interface have facilities for entering individual
dosing and conc histories and graphs of the predictions similar to
those that AbbotBase produces?
Nick
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Please save as .zip
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****
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.aaa.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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You might also consider ADAPT II. It requires a fortran compiler;
however, it runs in windows and is extremely flexible. Details of the
program and software download can be found at:
http://bmsr.usc.edu/Software/Adapt/adptmenu.html
USC*PACK as mentioned by Roger Jelliffe is another viable option.
Regards,
Paul Beringer, Pharm.D., BCPS, FASHP
USC School of Pharmacy
1985 Zonal Avenue
Los Angeles, CA 90033
Tel: 323-442-1402
eFax: 626-628-3024
Webpage: www.usc.edu/schools/pharmacy/antiinfective
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Dear Nick,
In response to your question on Bayesian Forecaster software: I am sorry
that I did not read the PharmPK messages for a few days, so I did not
reply
to your first message. Thanks to Johan Wallin for pointing to MW\Pharm.
MW\PHARM is a general clinical pharmacokinetic program including dosage
regimen calculation, parameter estimation based on measured plasma
levels
after any medication history, Bayesian feedback, population
pharmacokinetic
analysis, and many more.
The program has a database with pharmacokinetic parameters of about 180
drugs, but data of new drugs can be entered and stored unlimited.
Linear and
Michaelis-Menten elimination kinetics and 2- and 3-compartmental
models, in
any combination, are included.
The program calculates dosing regimens based on the therapeutic window,
pharmacokinetic parameters, and individual patient characteristics.
The medication history can take into account any dosing and sampling
schedule, changing creatinine level, changing body weight, and
extracorporeal clearance.
The program includes a module for population analysis based on an
Iterative
Two-Stage Bayesian procedure, which allows an easy, fast and reliable
generation of population parameters from the patient data stored in the
database.
MW\PHARM is widely used by hospital pharmacists in the Netherlands and
in
many other countries. An earlier version of the program has been
distributed
by Lilly for computer aided therapeutic drug monitoring of Vancocin
(vancomycin) and Obracin (tobramycin).
The current version MW\PHARM 3.50 is still a DOS-version but runs nicely
with Windows 98 and XP. We are working on a Windows version to be
released
at the end of 2004. A demo version (not yet including Bayesian
forecasting)
is available from Mediware.
The program is distributed by MediWare BV; for general info, trial
version,
prices and orders you can contact Eddy van Essen at vanessene.-a-.cs.com.
For technical/scientific questions you can contact me, the major
developer
of the MW\PHARM program.
Best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.aaa.farm.rug.nl
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Dear colleagues,
I was rather surprised by the message of NM, which contains some
pertinent
incorrect information on our software package MW\Pharm.
MW\Pharm is by no means 'outdated'. The program has been and is still
developed continuously, both with respect to the needs in clinical
practice
and to todays' scientific standards.
Although it runs under DOS, it works properly under Windows 98/2000/XP.
A
Windows version will be released later this year.
For more details please see my message sent earlier.
Finally, I want to stress that there have never been 'major scientific
problems'.
Best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.-a-.farm.rug.nl
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Dear Nick,
I can say that I do not have any experience with the Abbott program. I
can however state that we are rather flexible in inputting dose and
concentration histories. The interface is using NONMEM as the engine
but the user never needs (but he can) to interact with NONMEM. Libraries are
doing the job and each hospital can created their own databases for each drug
and make automated covariate searches on it, making better predictions
possible for new patients as they come in.
So I can not state that NONMEM does a better job than the Abbott
package, nor can I state that NONMEM is better or worse than other packages like
the Jellife package or Adapt. Those are endless scientific discussions. I
was only referring to one package and only to version below version 3.
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)