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:n.holford > http://www.health.auckland.ac.nz/pharmacology/staff/nholford/ > >