PRED in a Hill binding model

From: Toufigh Gordi <tgordi@buffalo.edu> Subject: [NMusers] PRED in a Hill binding model Date: 6/18/2003 5:06 PM Dear all, I have a simple cell binding model (Hill equation). The PK parameters where estimated separately and then individual PK estimates (2-comp, nonlinear CL) were fixed (entered in the underlying PD data set). The model file is given below. It works nicely and gives reasonbale estimates of the parameters. One thing that puzzles me, however, is that the population predictions (PRED) are NOT the same for subjects in the same dose group (6 subjects each in 6 different single dose groups). The question is then, what PRED is and also how I get the population estimates? Regards, Toufigh Gordi $PROB ALL DOSES ; 2-COMP $INPUT ID AMT RATE DUR DATE=DROP TIME DV EVID SEXF CMT GRP PKPD PKKM PKVM PKV1 PKQ PKV2 PKE1 PKE2 $DATA pd.csv IGNORE=# $SUBROUTINE ADVAN6 TRANS1 TOL=5 $MODEL NCOMP=2 COMP=CENT COMP=PERIPH $PK VM=PKVM*EXP(PKE1) KM=PKKM V1=PKV1*EXP(PKE2) Q=PKQ V2=PKV2 D1=DUR S1=V1 BASE=THETA(1) IMAX=THETA(2)*EXP(ETA(1)) IC50=THETA(3)*EXP(ETA(2)) HILL=THETA(4) $DES CON=A(1)/V1 DADT(1)=-A(1)*(VM/(KM+CON))/V1-A(1)*Q/V1+A(2)*Q/V2 DADT(2)=A(1)*Q/V1-A(2)*Q/V2 $ERROR CONC=F LAM=BASE-(IMAX*(CONC**HILL)/(IC50**HILL+(CONC**HILL))) Y=LAM*(1+EPS(1))+EPS(2) $THETA (0, 62, 100) ;1 BASE $THETA (0, 60) ;2 IMAX $THETA (0, 0.7) ;3 IC50 $THETA (0, 1) ;4 HILL $OMEGA 0.1 ;2 IIV BMAX $OMEGA 0.1 ;3 IIV IC50 $SIGMA 0.1 ;1 PROP ERROR $SIGMA 0.1 ;2 ADD ERROR $ESTIMATION NOABORT POSTHOC MAXEVAL=9999 PRINT=3 METHOD=1 MSFO=MSF2508 $COVARIANCE $TABLE ID TIME Y PKPD NOPRINT ONEHEADER FILE=SDTAB2508 $TABLE ID TIME BASE IMAX IC50 HILL ETA1 ETA2 NOPRINT ONEHEADER FILE=PATAB2508 $TABLE ID SEXF NOPRINT ONEHEADER FILE=CATAB2508 $TABLE ID GRP NOPRINT ONEHEADER FILE=COTAB2508