PharmPK Discussion - Pharmacodynamic modeling of multiple drugs

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On 30 Jul 2003 at 15:32:42, "Nathan Lack" (nlack.aaa.anormed.com) sent the message


The following message was posted to: PharmPK

Hi all,

I am curious if it is possible to create an integrated pharmacodynamic
model for two separate drugs that have similar effects. Any examples
would be appreciated.

Regards,

Nathan Lack
AnorMED Inc.

[Should be possible, model the PK/PD for each drug and 'add' the
effects together. The 'add' may be more complex if synergy etc.
interesting idea - db]

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On 30 Jul 2003 at 20:08:30, GLDrusano.-a-.aol.com sent the message


The following message was posted to: PharmPK

HI!

Our group examined the combined antiretroviral effect of abacavir plus
amprenavir. In the first paper, in AAC, the Greco model was applied to
the data and point estimates of the drug interaction model were
obtained (at that time, abacavir was 1592U89 and amprenavir was
141W94). Later, population PK analysis was performed for both drugs and
Monte Carlo simulation was performed to look at combined effects linked
to PK. This was also in AAC. Hope this helps.

George Drusano

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On 30 Jul 2003 at 17:13:51, Roger Jelliffe (jelliffe.at.usc.edu) sent the message


Dear Nathan:

Of course. All you have to do is to define the structural
model(s) you with to evaluate, and to model the relationship between
the serum concentrations (or concentrations on other, tissue, for
example, compartments), and the observed effect(s). Once the structural
model(s) have been defined by their differential equations, software
(or you) can white the Fortran source code for them in a form that can
be used by our NPAG software to make the population model. This model
will have quite a number of compartments and parameters, so it will be
computationally intensive. The USC*PACK software is designed for this,
and its results are consistent, in contrast to much of the parametric
modeling software, which is not.

You can go to our web site www.lapk.org, and click on New
Advances in Population Modeling, and see the presentation given by Bob
Leary at the PAGE meeting in Paris in 2002. Let me know if you want to
do more.

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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On 31 Jul 2003 at 09:06:20, (moate.-at-.cahp.vet.upenn.edu) sent the message


The following message was posted to: PharmPK

To Nathan,
   certainly. There are many examples of this
in the book by: Gabrielsson J and D Weiner.
1994 Pharmacokinetic and
Pharmacodynamic Data Analysis: concepts
and applications. SwedishPharmaceutical
Press, Stockholm.
  These types of systems with interactions
between drugs can easily be implemented
in WinSAAM. WinSAAM can be
downloaded free from the internet from
WinSAAM.com
Best wishes,
Peter Moate

  Peter J. Moate
Research Associate
University of Pennsylvania,
School of Veterinary Medicine,
Biostatistics Section, Clinical Science,
New Bolton Center, 382 W. Street Road.
Kennett Square, PA 19348
      Phone: 610-444-5800 Ext. 2146
      Fax:   610-925-8123
Work Email: Moate.-a-.cahp2.nbc.upenn.edu

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On 31 Jul 2003 at 15:01:04, Prasad Kambhampati (Prasad.Kambhampati.-at-.mdsps.com) sent the message
```
Dear Nathan Lack,

Try CombiTool software.

http://www.imb-jena.de/www_bioc/CombiTool/

Prasad Kambhampati
```
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