PD interaction between two substances

From: Johan.Rosenborg@astrazeneca.com Subject: [NMusers] PD interaction between two substances Date: Mon, April 5, 2004 8:01 am All, I would like to model a pharmacodynamic interaction between two substance - denoted "1" and "2" below - assumingly with a common Emax-value but with different EC50-values - EC50(1) and EC50(2) - using the equation below (adapted from a text book on receptor theory by T P Kenakin): Effect = Emax X {1/(1 + EC50(1)/[C(1)] X (1 + [C(2)]/EC50(2)) + 1/(1 + EC50(2)/[C(2)] X (1 + [C(1)]/EC50(1))}, where Effect =Total effect of substance 1 and substance 2 Emax =Common maximum effect of substance 1 and substance 2 EC50(1)=Concentration of substance 1 giving half maximum effect EC50(2)=Concentration of substance 2 giving half maximum effect C(1) = concentration of substance 1 C(2) = concentration of substance 2 My question: There are several examples in the NONMEM help guide on how to transform PK- to PD-data under $ERROR in the model file using one PK-variable (PK_PD_simultaneous_1-4), but how can I do my case with two PK-variables? Johan Johan Rosenborg AstraZeneca R&D Lund Experimental Medicine, S-221 87 Lund, Sweden Tel: +46 46 33 65 99 Fax: +46 46 33 71 91 E-mail: johan.rosenborg@astrazeneca.com