From: "Gordi, Toufigh" Toufigh.Gordi@cvt.com Subject: [NMusers] Simulated PD value at time zero Date: Tue, February 1, 2005 1:45 pm Dear all, I am simulating an indirect response model with drug concentrations (following a tri-exponential decrease) decreasing the production rate of the effect. Part of the code is presented here: $PK ... BASE=KIN/KOUT S2=VC F1=BAV F5=BASE $DES ... CONC=A(2)/VC HIT=IEFF*CONC/(IC50+CONC) ... DADT(5)=KIN*(1-HIT)-A(5)*KOUT What seems strange to me is that the simulated value for compartment 5 (the effect) is equal to 0 and not BASE at time 0 (dose given at time 0.001). I have tried simulation data files with and without a value of 1 as dose for compartment 5 but the results are the same. Sufficient time after dose, the PD value returns and stays at the BASE value. Also in the actual NONMEM run, the initial value is equal to BASE. Any suggestions why the 0 time values for the PD are predicted to 0 and not BASE? Toufigh Gordi _______________________________________________________ From: "AbuTarif, Malaz" malaz.abutarif@spcorp.com Subject: RE: [NMusers] Simulated PD value at time zero Date: Tue, February 1, 2005 3:55 pm Dear, I think this is similar to what Max was asking earlier in the week [NMusers] Indirect response PD model. Without the drug, baseline PD is basically a steady state situation. NonMem does not know that. So, the solution to your problem is exactly the solution to Max's problem, I think. Initialize the effect or PD compartment with a bolus "PD dose" so it starts from ss conditions level (baseline), or define the effect compartment as a ss situation. Malaz Malaz A. AbuTarif, B.Sc. (Pharmacy), Ph.D., G.C.P.M. Associate Principal Scientist Schering-Plough Research Institute 2015 Galloping Hill Rd., K15-2-2650 Kenilworth, NJ 07033 Tel: (908) 740-3835, Fax: (908) 740-2916 malaz.abutarif@spcorp.com _______________________________________________________