RE: Dual inhibitor synergy model

________________________________________ From: [email protected] [[email protected]] on behalf of Mark Sale - Next Level Solutions [[email protected]] Sent: Tuesday, March 06, 2012 10:49 PM To: [email protected] Subject: RE: [NMusers] 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 President, Next Level Solutions, LLC www.NextLevelSolns.com 919-846-9185 A carbon-neutral company See our real time solar energy production at: http://enlighten.enphaseenergy.com/public/systems/aSDz2458 -------- 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