Predicting Drug in Tissue A2 using MAXEVAL=0

Title: Paul R Colleagues: I am working with a local investigator to estimate the effects of daily vs weekly dosing of an antibody. As such, I would like to show the expected amounts of drug in the two tissue compartments (A(2) and A(3)). The problem is that using MAXEVAL=0 and the same initial estimates, I get different values for the first dose, which should be equal for both the daily and weekly dosing. IPRED in plasma is different for each dosing regimen, but of course PRED gives the same end of infusion concentration. How can I code my model so that I can report out the amount of drug in each respective tissue compartment so that after dose 1 it is the same for the weekly and daily dosing? ( That is, how can I code it so that A(2) after the first weekly dose is the same as A(2) after the first of the daily doses.) CTL follows. Thank you! Paul $DATA ..\Qwk_60mg_sim.csv IGNORE=# $SUBROUTINES ADVAN6 TOL=3 $MODEL NCOMP=3 NPAR=8 COMP=(CENTRAL DEFDOSE DEFOBS) COMP=(TISU1) COMP=(TISU2) $PK F1=1 IF(DOS1.EQ.40) F1=THETA(8) TVCL=THETA(1) TVV1=THETA(2) TVQ1=THETA(3) TVV2=THETA(4) TVQ2=THETA(5) TVV3=THETA(6) CL=TVCL*EXP(ETA(1)) V1=TVV1*EXP(ETA(2)) Q1=TVQ1 V2=TVV2 Q2=TVQ2 V3=TVV3 S1=V1 K10= CL/V1 K12= Q1/V1 K21= Q1/V2 K13= Q2/V1 K31= Q2/V3 $DES DADT(1) = -A(1)*(K10 + K13 + K12) + K21*A(2) + K31*A(3) DADT(2) = A(1)*K12 - A(2)*K21 DADT(3) = A(1)*K13 - A(3)*K31 A2=A(2) A3=A(3) $ERROR W1=THETA(7) IPRED = LOG(0.025) W = SQRT(W1**2) IF(F.GT.0) IPRED = LOG(F) IRES = IPRED-DV IWRES = IRES/W Y=IPRED+ W * EPS(1) OBSV=EXP(DV) $THETA 0.687; POPCL $THETA 1.19 ; POPV1 $THETA 6.87; POPQ1 $THETA 1.8 ;POPV2 $THETA 0.191; POPQ2 $THETA 29.6; POPV3 $THETA 0.393; W1 $THETA 0.631; F1 $OMEGA BLOCK(2) 1.47E-01 ; IIVCL 1.87E-01 7.03E-01 ; IIVV $SIGMA 1 FIX ; ERR_CHLO $EST MAXEVAL=0 METHOD=COND POSTHOC NOABORT PRINT=1 $TABLE ID TIME IPRED A2 A3 NOPRINT ONEHEADER FILE=SimOut.fit -- Paul R. Hutson, Pharm.D. Associate Professor UW School of Pharmacy 777 Highland Avenue Madison WI 53705-2222 Tel 608.263.2496 Fax 608.265.5421 Pager 608.265.7000, p7856