Drug PD interaction model

Dear Nonmem users, I am looking for a model or a paper where it is reported that describes the interaction of three drugs, which act on the same PD parameter, however, two of them via independent mechanisms, whereas the third shares the mechanism of action, e.g., receptor, with one of the first two drugs. Any help, reference or direct modelling support, is appreciated and thanked for in advance. Best wishes Jorn Lotsch -- _______________________________________________________ Univ.-Prof. Dr. med. Jörn Lötsch pharmazentrum frankfurt/ZAFES Institut für Klinische Pharmakologie Goethe-Universität Theodor-Stern-Kai 7 D-60590 Frankfurt am Main Tel.:069-6301-4589 Fax.:069-6301-7636 http://www.klinik.uni-frankfurt.de/zpharm/klin/

Hello Jon, I believe that there should be examples of this in the HIV literature. My colleague, Joy Feng, published on this topic recently: "The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study" Feng, J.Y. et al. (2009) Retrovirology 6:44 This may not be exactly what you want as tenofovir and emtricitabine are both nuc inhibitors of HIV reverse transcriptase, while efavirenz targets the same enzyme but in a different manner. There may be similar papers out there, where the third drug has a different target (e.g. HIV protease). All the very best, Bernard Bernard Murray, Ph.D. Senior Research Scientist, Drug Metabolism Gilead Sciences, Foster City CA

Dear Jorn, The 2 drugs acting on the same receptor you can model using basic receptor pharmacology. That interaction should be fairly predictable. The third drug I would introduce using some semi-mechanistic model, dependent on how much you know. Do you have a lot of data? I would stay clear from anything that models "synergism". Bart Bart Laurijssens BEL Pharm Consulting Moulin d'Ozil, Chambonas 07140, France Phone: +33 (0)685 16 55 94 [email protected] > Message du 27/07/10 21:12 > De : "Jorn Lotsch" > A : "[email protected]" > Copie à : > Objet : [NMusers] Drug PD interaction model > > Dear Nonmem users, > > I am looking for a model or a paper where it is reported that describes > the interaction of three drugs, which act on the same PD parameter, > however, two of them via independent mechanisms, whereas the third > shares the mechanism of action, e.g., receptor, with one of the first > two drugs. Any help, reference or direct modelling support, is > appreciated and thanked for in advance. > > Best wishes > > Jorn Lotsch > > -- > > _______________________________________________________ > Univ.-Prof. Dr. med. Jörn Lötsch > pharmazentrum frankfurt/ZAFES > Institut für Klinische Pharmakologie > Goethe-Universität > Theodor-Stern-Kai 7 > D-60590 Frankfurt am Main > > Tel.:069-6301-4589 > Fax.:069-6301-7636 > http://www.klinik.uni-frankfurt.de/zpharm/klin/ > > > > > >