Simulated PD value at time zero

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