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Several people have posted asking me to list the references I received
and the programs on my evaluation list. Here they are.
Please note that the list is in no particular order, and not all programs are
necessarily equivalent - this is just what I got back from the group.
I'm not sure if it's kosher to include Email addresses, but have assumed
that if someone is providing a product they don't mind being contacted...
[my apologies if this is not the case]
The best all-around source for this information is still
www.cpb.uokhsc.edu/pkin/soft.html
but I was only interested in IBM-PC-WIN3.x-MSExcel-compatible
programs, which is a much smaller window.
1. T.D.M.S. [I haven't received this yet, but it's probably gone astray in the
mail] from Philip_Anderson.at.SANDMAIL.ucsd.edu - if you're out there,
Phil, I apologize to you for not having included my full mailing address:
P.O. Box 5904, LCD Merivale, Ottawa, ON K2X 3X7, Canada - I was only
expecting Email responses.
2. MultiForte & Boomer from David Bourne [david-bourne.aaa.uokhsc.edu]
[love that kangaroo!]
3. "Fit-Regression" from WindowChem Software
[www.windowchem.com], a product which we purchased as an Excel
add-on]
4. NCOMP from Paul Laub [plaub.at.draco.rm.fccc.edu]
5. PKAnalyst from Micromath [www.micromath.com] - they also have a
product called Scientist with PK add-ons, but it doesn't look too different
from PKAnalyst based on the demos I downloaded from their site
6. WinNonlin from Scientific Consulting Inc.
[75450.3171.at.compuserve.com] who have a video demo rather than an
interactive one. This product follows on from PCNONLIN, which I have
used before.
7. SAAM from NIH [www-saam.nci.nih.gov/saam.htm] as recommended
by Robert Phair
There are a few other leads I haven't followed up on yet:
ACSL BioMed and Optimize at www.mga.com
Kinetica [by Simed] at www.bioscience.com
PCMODFIT [contact Alan Thawley, alan.-a-.artpac.demon.co.uk]
METABASE & PK SOLUTIONS at www.bright.net/~dfarrier/index.html
Prices of the above range from zero to ridiculous! I have not yet looked
at them all, so I have no comments to make on any.
Once again, my thanks to everyone who responded, and I hope all of my
transcriptions and citations are accurate.
Adrienne Stevenson
Ottawa, Canada
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Thanks for the list of PK programs you are evaluating. Since you
specifically mention Excel, you might consider looking at PKPD Tools
for Excel with XLMEM. This is a public domain Excel spreadsheet by
Charles Minto and Thomas Schnider. You can find it on my WWW site:
http://pkpd.icon.palo-alto.med.va.gov
One interesting aspect to this is the implementation of mixed effect
modeling, using the NONMEM objective function (first order approximation),
in a dynamic link library accessible to Excel. The function returns
the same values as all of the NONMEM test sets, with comparable execution
times (the code is compiled). However, it is limited to the series of
models implemented in PKPD tools, and thus has neither the flexibility
nor the more recent objective functions (e.g., conditional estimation)
implemented in NONMEM. At present, it is a prototype of a more complete
population analysis tool with Excel that Drs. Minto and Schnider hope
to build.
Unfortunately, our local VA has perpetual problems with its network,
so access may or may not work. However, if it does, PKPD Tools should
be interesting. It is still evolving, with major updates every 6-8
months, as Drs. Minto and Schnider have time to make additions.
Steve Shafer
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SAAM from the NIH is a good package that has been in use for decades, but
my actual
kinetics software recommendation to Adrienne Stevenson was for SAAM II with an
intuitive graphical user interface and a bunch of hotshot peer-reviewed
optimizer
algorithms and flexible weighting schemes. You can find out more about SAAM
II from the
SAAM Institute (1.800.421.SAAM) or the Resource Facility for Kinetic
Analysis at the
University of Washington:
http://weber.u.washington.edu/~rfka/
Regards,
Bob
--
Robert D Phair PhD: rphair.aaa.ix.netcom.com
BioInformatics Services: http://www.webcom.com/rphair
Partnering and Outsourcing for Computational Biology
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Thanks to Bob Phair for clarifying the information I had in my "list".
I had not followed the link he notes, but I will!
Adrienne
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Dear all,
I am interested in getting a moderately priced PK analysis package which is
Windows compatible. I have seen the demo versions of Scientist and
PKanalyst from Micromath. They appear slightly similar although my
understanding is that in Scientist there is greater flexibility for the
model equations (simultaneous differential, Laplace etc) as well as the
possibility of fitting simultaneously data of other metabolites or
concentrations in other compartments which would be useful for my work. I
would like to know if anyone out there has purchased and used either of
these packages and whether they found significant hickups. Any comparisons
of these and better/worse PK packages would be welcome. In the past, I
have done my fitting with a combination of Sigmaplot, the free listing of
Yamaoka K et al J. Pharmacobio-Dynam 4:879-885, 1981, and the method of
using EXCEL for non-linear curve fitting described by Bowen and Jerman, TIPS
16:413-417, 1995.
Sigmaplot is OK for simple equations, the Yamaoka program is extremely
versatile and with some re-writing can load/save info to disc (however it is
a B/W dinosaur) and the EXCEL method is good for enzyme, cytotoxicity and PD
work but is out of the question for serious PK work. Time to go upmarket
and get something more presentable.
I look forward to hearing from someone!
Laurent P Rivory
Department of Medicine
University of Queensland
Princess Alexandra Hospital
Ipswich Rd, Woolloongabba 4102
QLD, Australia
Email: Lrivory.-at-.gpo.pa.uq.oz.au
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All the programs you mentioned are a variation on the theme of curve
fitting. The short coming as I see it (and I hope others might share their
own viewpoints on this) is that programs such as these give good equations
and curve fits but provide little in the way of useful PK parameters.
Typically they give little more than the AUC, half-life and lag-time. On the
other hand, when one surveys, for example, Drug Metabolism and Disposition,
the vast majority of papers dealing with pharmacokinetics provide tables
which include these and other PK parameters (such as the Vd, Cl, MRT, AUMC,
etc.) as their primary results. Typically, these results are all based on
non-compartmental assumptions. I tabulated the contents of 2 years of DMP
issues to arrive at this fact. It appears that compartmentalists need
equations, but practitioners need parameters. To fill the void in software,
I developed a program called PK Solutions. It runs in Excel and is automated
with VBA procedures. It calculates about 25 parameters for blood levels
obtained after single oral or iv bolus and predicts an additional 25 steady
state parameters based on multiple dosing. It provides curve stripping
and/or Excel Solver-based curve fitting of time-concentration data, or one
can supply exponential terms derived from other software (i.e., curve
fitting software).
PK Solutions could use some usability testing in order to insure it meets
the right niche of user needs. If you are interested, I could provide you
(and other readers) with a demo copy in exchange for your cherished feedback.
David
Dr. David S. Farrier
Summit Research Services
1374 Hillcrest Drive
Ashland, OH 44805 USA
(419)-289-9207
E-mail: dfarrier.-at-.bright.net
Internet: http://www.bright.net/~dfarrier/
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About Laurent Rivory's question about PK analysis packages:
I suggest considering ADAPT II, the PKPD simulation and fitting program
written by DZ D'Argenio and A Schumitzky and available at little or no cost
from the Biomedical Simulations Resource at the University of Southern
California. I have heard that a Windows version of ADAPT II is nearing
completion; in the meantime an excellent DOS version exists and has a devoted
following (myself included).
Advantages of ADAPT II:
1. Enormous flexibility, in that you write the equations or differential
equations describing the system as well as the variance function
describing the presence of noise or error.
2. Statistical features not found in other packages such as fitting using
Bayesian priors as well as support for designing optimal sampling.
3. The program comes as well documented FORTRAN 77 source code, so that if
you absolutely have to, you can "look under the hood" and find out how
the program works.
4. Track record - the program has been around since 1979 and has many
users worldwide; the authors at USC regularly hold conferences or
training courses on ADAPT (as they did last May).
Disadvantages of ADAPT II:
1. Enormous flexibility - maybe too much for someone learning pharmacokinetics.
Additionally, flexibility assumes basic knowledge of writing
FORTRAN code as well as compiling and linking FORTRAN programs.
2. Requires a FORTRAN compiler, so that while ADAPT II is free (at least to
academic users), the compiler is not. But in a lab where lots of number
crunching is going on, a FORTRAN compiler may find many other uses.
3. Lack of a slick interface (the DOS version; the Windows version may be
different). Programs that are point and click are nice UNTIL you want
to do something even slightly different from what the program's authors
had in mind. Then your hands are tied ... but not with ADAPT II.
>PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
>Dear all,
>I am interested in getting a moderately priced PK analysis package which is
>Windows compatible. I have seen the demo versions of Scientist and
>PKanalyst from Micromath. They appear slightly similar although my
>understanding is that in Scientist there is greater flexibility for the
>model equations (simultaneous differential, Laplace etc) as well as the
>possibility of fitting simultaneously data of other metabolites or
>concentrations in other compartments which would be useful for my work. I
>would like to know if anyone out there has purchased and used either of
>these packages and whether they found significant hickups. Any comparisons
>of these and better/worse PK packages would be welcome. In the past, I
>have done my fitting with a combination of Sigmaplot, the free listing of
>Yamaoka K et al J. Pharmacobio-Dynam 4:879-885, 1981, and the method of
>using EXCEL for non-linear curve fitting described by Bowen and Jerman, TIPS
>16:413-417, 1995.
>Sigmaplot is OK for simple equations, the Yamaoka program is extremely
>versatile and with some re-writing can load/save info to disc (however it is
>a B/W dinosaur) and the EXCEL method is good for enzyme, cytotoxicity and PD
>work but is out of the question for serious PK work. Time to go upmarket
>and get something more presentable.
>
>I look forward to hearing from someone!
>
>Laurent P Rivory
>Department of Medicine
>University of Queensland
>Princess Alexandra Hospital
>Ipswich Rd, Woolloongabba 4102
>QLD, Australia
>Email: Lrivory.at.gpo.pa.uq.oz.au
Paul (Sisyphus) B. Laub mathematical modeling of biomedical data
Dept. of Medical Oncology 328 West Bldg.
Fox Chase Cancer Center 7701 Burholme Ave. Phila. PA 19111 USA
p_laub.aaa.fccc.edu (215)728-4743 (voice) (215) 728-2741 (fax)
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We use SCIENTIST a lot and are very happy with it. It is easy to use
and has nice graphics.
Prof. Dr. Hartmut Derendorf
University of Florida
100494, College of Pharmacy
Gainesville, FL 32610
HARTMUT.-at-.COP.HEALTH.UFL.EDU
Phone (352)846-2726
Fax (352)392-3249
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Laurent-
As I have said in response to two recent queries like yours, you owe it to
yourself to
check out SAAM II from the SAAM Institute Inc, in Seattle Washington, USA.
You can
reach them at 1.800.421-SAAM or you can visit their website at
http://weber.u.washington.edu/~rfka/
There is a downloadable demo version on the website.
I've been in the kinetics business for almost 30 years and I'm now doing
all my work in
SAAM II. It's got a neat graphical user interface, runs under Win95, WinNT,
or MacOS,
has a bunch of hot-shot integration and parameter estimation algorithms,
and it's not
very expensive. I've used the software to teach kinetics to more than 100
people in the
last three years, and they have been unanimous in their praise for how easy
it is to
learn.
If you take a look at SAAM II, please let me know what you think.
Regards,
Bob
--
Robert D Phair PhD: rphair.-at-.ix.netcom.com
BioInformatics Services: http://www.webcom.com/rphair
Partnering and Outsourcing for Computational Biology
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> All the programs you mentioned are a variation on the theme of curve
> fitting. The short coming as I see it (and I hope others might share their
> own viewpoints on this) is that programs such as these give good equations
> and curve fits but provide little in the way of useful PK parameters.
> Typically they give little more than the AUC, half-life and lag-time. On the
> other hand, when one surveys, for example, Drug Metabolism and Disposition,
> the vast majority of papers dealing with pharmacokinetics provide tables
> which include these and other PK parameters (such as the Vd, Cl, MRT, AUMC,
> etc.) as their primary results. Typically, these results are all based on
> non-compartmental assumptions.
I have to disagree with your conclusion as a general shortcoming about
'curve fitting' programs. Any general non-linear regression program that
allows the user to define the model will also allow any
parameterisation the user wants. There is nothing to stop you
parameterising a model in terms of Vd and CL (as opposed to elimination
rate constants [like alpha and beta] and 'intercepts' [like A and B].
Unfortunately I suspect many of the programs you mention were not
developed or maintained by pharmacokineticists and so they offer a
general 'mathematical' parameterisation without understanding the nature
of the application of PK models as a tool to understand biology.
AUC and AUMC have no intrinsic merit as PK parameters. They are simply
intermediate values which are usually obtained via non-compartmental
methods and then applied to obtain the PK parameters of real interest
i.e. CL and Vss.
I would say that most PK analysts today have moved away from the old A,
alpha, B, beta, and the K1O, K12, K21, V parameterisations of the two
compartment model and now favour parameters that are more closely
related to structure and function i.e CL, Vss, CLic (inter-compartmental
clearance) and V (central cpt volume).
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, Private Bag 92019, Auckland, New Zealand
email:n.holford.-a-.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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Hi everyone:
I would like to find out if anyone has information about US lab which
can provide analytical service for 2D6 genotyping and phenotyping for
clinical studies.
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