metabolite modelling

From: "Wixley, Dick" <Dick.Wixley@solvay.com> Subject: metabolite modelling Date: Thu, 9 Dec 1999 15:49:59 +0100 Dear users, I am trying to simultaneously model parent compound and metabolite. Oral dosing - a 2-compartment model describes the parent compound well. I have used the following code. It converged but took a long time but I was not impressed with the results. I would be interested in references on how to taCkle this problem. My next step will be to do a sequential fit. I am concerned that I may be making some basic errors in my model definition. Many thanks for your help. Dick Wixley $PROBLEM metabolite and parent compound $INPUT SUBJ=ID DOSE=AMT TIME CPLA=DV TRT EVID MDV MDD QT PR CMT $DATA y:\a_pk_pd\ted_ver\data\nmnor1\NOR2sim IGNORE=C $SUBROUTINES ADVAN7 $MODEL COMP = (DEPOT DEFDOSE INITIALOFF) COMP = (CENTRAL DEFOBS) COMP = PERIPH COMP = (METAB ) $PK K12 =THETA(1)*EXP((ETA(1))) K23 =THETA(2)*EXP((ETA(2))) K32 =THETA(3)*EXP((ETA(3))) K24 =THETA(4)*EXP((ETA(4))) K40 =THETA(5)*EXP((ETA(5))) K20 =THETA(6)*EXP((ETA(6))) V2 =THETA(7)*EXP((ETA(7))) V4 =THETA(8)*EXP((ETA(8))) S2=V2 /1000 s4=V4/1000 ALAG1 = THETA(9)*EXP(ETA(9)) $ERROR FX=0 IF(F.EQ.0) FX=1 W=F+FX IF (CMT.EQ.4) THEN Y = F*EXP(ERR(2)) ELSE Y = F*EXP(ERR(1)) ENDIF IPRED=F IRES=DV-IPRED IWRES=IRES/W $THETA (0,3.4) (0,.24) (0,.13) (0,.27) (0,.13) (0,21) (0,290) (0,0.9) (0,0.5) $OMEGA 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 $SIGMA 0.25 0.25 $ESTIMATION MAXEVAL=9999 PRINT=5 SIGDIGITS=4 POSTHOC MSFO=RUN5I.MSF $COVARIANCE $TABLE ID TIME DOSE ALAG1 K12 K23 K32 K24 K40 K20 V2 V4 CMT IPRED DV PR QT NOPRINT FILE=rmetab2 ONEHEADER