RE: NONMEM Modeling of Plasma + Urine Data

From: "Nandy, Partha [PRDUS]" PNandy@prdus.jnj.com Subject: RE: [NMusers] NONMEM Modeling of Plasma + Urine Data Date: Wed, 22 Nov 2006 19:23:38 -0500 Hi Tarek, I am assuming that the drug is given as an infusion from the "RATE" column in your data file. You mentioned that you ran the model with just the parent & metabolite data in plasma. Did you use ADVAN7 for that as well? The formation of metabolite is not well defined..Is it a saturable process? If so, Km and Vmax should be implemented. Also, TVCL is total clearance as shown below: TVCL = THETA(1) CL = TVCL*EXP(ETA(1)) So, it is not clear how the following is implemented.. TVCLM = THETA(5) CLM = TVCLM * EXP(ETA(5)) Usually Total Clearance is modeled as CL=CLRenal + CLMetab Just quickly browsing through the data I do not see rate being declared in your control file as R1=RATE. Curious about how the RATE was specified in the control file when the parent & metab concentration in plasma was modeled. I also see that V1 and V3 was scaled but not V2. Your error structure is quite complex. It is not clear to me what the purpose of ERR(4) is. Also your initial conditions for SIGMA seems to be very high! Typically the ERROR could be modeled as (There are many ways to do this..). I1=0 I2=0 I3=0 I4=0 IF (CMT.EQ.1) I1=1 IF (CMT.EQ.3) I2=1 IF (CMT.EQ.4) I3=1 IF (CMT.EQ.5) I4=1 Y=IPRED + I1*ERR(1) + I2*ERR(2) + I3*ERR(3) + I4*ERR(4) Instead of just additive model, did you try other ERROR models for e.g. ADD+PROP etc? Hope this helps. Partha _______________________________________________________