NONMEM Users Network Archive

Hosted by Cognigen

Re: parent drug and metabolite

From: Leonid Gibiansky <leonidg>
Date: Sun, 04 Mar 2007 23:21:56 -0500

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/
>
>
Received on Sun Mar 04 2007 - 23:21:56 EST

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.