Indirect response model in NONMEM

From: "Gordi, Toufigh" Toufigh.Gordi@cvt.com Subject: [NMusers] Indirect response model in NONMEM Date: Wed, August 25, 2004 5:04 pm Dear all, I am trying to fit an indirect response model (decrease in KIN) to some data. I have fairly good data, including pre-dose observations. There were three different dosings: oral, iv bolus and iv bolus+iv infusion. The PK part is fixed based on individual PK estimates. This is a sample of the model code: $SUBROUTINE ADVAN9 TRANS1 TOL=5 $MODEL NCOMP=5 COMP = (GUT) COMP = (CENT) COMP = (PRIPH) COMP = (PER2) COMP = (EFF) $PK CL=CL1 ... IEFF=THETA(1) IC50=THETA(2)*EXP(ETA(1)) KOUT=THETA(3) KIN=THETA(4) S2=VC D2=DUR F1=BAV $DES ... CONC=A(2)/VC HIT=IEFF*CONC/(IC50+CONC) ... DADT(5)=KIN*(1-HIT)-KOUT*A(5) Could anybody give me some guidance on how the data file should be constructed? And how the data file and the control stream should be modified in case I want to estimate a baseline value? I have found some previous comments on "initializing" the effect compartment but have not been able to make it work. Thank you! Toufigh Gordi