RE: Dual inhibitor synergy model
Mads,
You might start with some of the work of Chou and Talalay. Here is a
recent paper on study design
Drug Combination Studies and Their Synergy Quantification Using the
Chou-Talalay Method Ting-Chao Chou
In Cancer Res January 15, 2010 70; 440
It is based on some pretty old work on quantifying synergy. Bottom line,
it is really, really hard, requiring nearly a full-grid of doses (e.g.,
16 doses, a 4x4 matrix of doses). Stella Machado also did some work,
slightly different synergy model, here is an example.
Analysis of Antimalarial Synergy between Bestatin and Endoprotease
Inhibitors Using Statistical Response-Surface Modelling by Clare S
Gavigan, Stella G Machado, John P Dalton, Angus Bell
Antimicrobial Agents and Chemotherapy (2001)
Volume: 45, Issue: 11, Publisher: American Society for Microbiology,
Pages: 3175-3181
Mark Sale MD
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Quoted reply history
-------- Original Message --------
Subject: [NMusers] Dual inhibitor synergy model
From: Mads Kreilgaard <[email protected]>
Date: Tue, March 06, 2012 4:02 pm
To: "[email protected]" <[email protected]>
I am looking for an appropriate design and modeling strategy for
inhibition of levodopa-induced dyskinesia (LID) in a rat model of
Parkinsons disease. Dyskinesia (AIM) is scored categorically 0,1,2,3 or
4. The two active drugs by them selves only have a minor maximum
response in the model (reversal of AIMS), but displays synergy when
combined. My intended PKPD study design is maintaining a relative
constant dyskinesia level with levodopa, and combine three doses each
(low, medium, high) of the inhibitory drugs A and B, in a total of 9
treatments in addition to a levodopa baseline study.
With respect to the modeling strategy, my intention is to establish a
baseline model for levodopa-induced dyskinesia. Do you have
suggestions/literature references for models that could be applied to
analyse the synergistic inhibitory responses of drug A and B?
Best regards,
Mads