Re: parent drug and metabolite

I cannot see any problems with the equations, looks correct to me: K=CL1/V1 DADT1=-K*A(1) S1=V1 etc. Leonid Nick Holford wrote: > Sam, > > There is no problem with using CL1 in this code. This is not a reserved word > and CL is not a required variable name when using $DES. > > I fixed the more obvious errors so that the following code will run with > NM-TRAN. However, the equations for parent and metabolites dont make sense to > me. It looks like Amounts are being multiplied by volumes when they should be > divided in order to get concentration. > > Nick > > $PROBLEM Parent drug & active metabolite ;Units: Time=mins, ;Concentration=uM(umols/L), Amount=umols > > ;Age=yrs, Weight=kg > > $DATA AW2.CSV IGNORE=# $INPUT ID TIME DV ANUM AMT SEX=DROP WT AGE CMT > > $SUBROUTINE ADVAN6 TRANS1 TOL=5 > $MODEL > COMP=(PARENT) COMP=(METAB1) COMP=(METAB2) > > $PK > CL1=THETA(1)*EXP(ETA(1)) > V1=THETA(2)*EXP(ETA(2)) > K20=THETA(3)*EXP(ETA(3)) > Q=THETA(4)*EXP(ETA(4)) > V2=THETA(5)*EXP(ETA(5)) > V3=THETA(6)*EXP(ETA(6)) > S1=V1 > S2=V2 > K12=CL1/V1 > > $DES > DADT(1)=-CL1*A(1)/V1 > DADT(2)=CL1*A(1)/V1+Q/V3*A(3)-Q/V2*A(2)-K20*A(2) > DADT(3)=Q/V2*A(2)-Q/V3*A(3) > > $ERROR > W=F > IPRED=F > IRES=DV-IPRED > IWRES=IRES/W > P1=0 > IF(CMT.EQ.1)P1=1 > P2=0 > IF(CMT.EQ.2)P2=1 > Y1=W*(1+ERR(1)) > Y2=W*(1+ERR(2)) > Y=P1*Y1+P2*Y2 > > $THETA > (0,,100000) ; CL1 > (0,,100000) ; V1 > (0,,100000) ; K20 > (0,,100000) ; Q > (0,,100000) ; V2 > (0,,100000) ; V3 > $OMEGA > 0.1 ; PPV_CL1 > 0.1 ; PPV_V1 > 0.1 ; PPV_K20 > 0.1 ; PPV_Q > 0.1 ; PPV_V2 > 0.1 ; PPV_V3 > $SIGMA > 0.1 ; RUV_P > 0.1 ; RUV_M > > ;$ESTIMATION MAXEVAL=9999 PRINT=5 POSTHOC > ;$COVARIANCE > $TABLE ID TIME DV ANUM AMT WT AGE CMT EVID MDV IPRED IWRES > NOPRINT ONEHEADER FILE=OUTAMIWR.FIT > > Sam Liao wrote: > > > Hi Zheng: > > It is complaining the CL1. You need to replace all CL1 with CL. But > > you have other problems in your $INPUT statement and the data set too. > > > > Sam > > > > > Dear All: > > > > > > why do I get following error message with the following code? Any > > > opinions regarding this problem and code will be highly appreciated. > > > Thank you very much for your consideration and help. I am modeling > > > parent drug and active metabolite at the same time with this code. > > > > > > AN ERROR WAS FOUND IN THE CONTROL STATEMENTS. > > > > > > AN ERROR WAS FOUND ON LINE 13 AT THE APPROXIMATE POSITION NOTED: > > > CL1=THETA(1)*EXP(ETA(1)) > > > X > > > THE CHARACTERS IN ERROR ARE: > > > 202 FORTRAN SYNTAX IS INCORRECT OR INAPPROPRIATE IN THIS CONTEXT. > > > 4 > > > > > > $PROBLEM Parent drug & active metabolite ;Units: Time=mins, > > > Concentration=uM(umols/L), Amount=umols > > > ;Age=yrs, Weight=kg > > > $DATA AW2.CSV IGNORE=C $INPUT ID TIME DV ANUM AMT SEX WT AGE CMT EVID MDV > > > > > > $SUBROUTINE ADVAN6 TRANS1 TOL=5 > > > $MODEL > > > COMP=(PARENT) COMP=(METAB1) COMP=(METAB2) > > > > > > $PK > > > CL1=THETA(1)*EXP(ETA(1)) > > > V1=THETA(2)*EXP(ETA(2)) > > > K20=THETA(3)*EXP(ETA(3)) > > > Q=THETA(4)*EXP(ETA(4)) > > > V2=THETA(5)*EXP(ETA(5)) > > > V3=THETA(6)*EXP(ETA(6)) > > > S1=V1 > > > S2=V2 > > > K12=CL1/V1 > > > > > > $DES > > > DADT(1)=-CL1*A(1)/V1 > > > DADT(2)=CL1*A(1)/V1+Q/V3*A(3)-Q/V2*A(2)-K20*A(2) > > > DADT(3)=Q/V2*A(2)-Q/V3*A(3) > > > > > > $ERROR > > > W=F > > > IPRED=F > > > IRES=DV-IPRED > > > IWRES=IRES/W > > > P1=0 > > > IF(CMT.EQ.1)P1=1 > > > P2=0 > > > IF(CMT.EQ.2)P2=1 > > > Y1=W*(1+ERR(1)) > > > Y2=W*(1+ERR(2)) > > > Y=P1*Y1+P2*Y2 > > > > > > $THETA > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > $OMEGA > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > $SIGMA > > > (0,,0.1000E+07) > > > (0,,0.1000E+07) > > > > > > $ESTIMATION MAXEVAL=9999 PRINT=5 POSTHOC > > > > > > $COVARIANCE > > > > > > $TABLE ID TIME DV ANUM AMT SEX WT AGE CMT EVID MDV IPRED IWRES > > > NOPRINT ONEHEADER FILE=OUTAMIWR.FIT > > > > > > ID Time DV Anum AMT Gender WT Age CMT > > > 1 0 0 1 3371.43 F 110.23 44 1 > > > 1 1 187 1 0 F 110.23 44 1 > > > 1 1 14.24 1 0 F 110.23 44 2 > > > 1 5 85.55 1 0 F 110.23 44 1 > > > 1 5 28.49 1 0 F 110.23 44 2 > > > 1 15 12.1 1 0 F 110.23 44 1 > > > 1 15 13.43 1 0 F 110.23 44 2 > > > 1 30 1.03 1 0 F 110.23 44 1 > > > 1 30 3.25 1 0 F 110.23 44 2 > > > 1 45 1.19 1 0 F 110.23 44 2 > > > 1 60 0.83 1 0 F 110.23 44 2 > > > 1 120 0.4 1 0 F 110.23 44 2 > > > 1 180 0.35 1 0 F 110.23 44 2 > > > 1 240 0.13 1 0 F 110.23 44 2 > > > > > > Zheng > > -- > Nick Holford, Dept Pharmacology & Clinical Pharmacology > University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand > email:[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:373-7556 > http://www.health.auckland.ac.nz/pharmacology/staff/nholford/