Dear nmusers-team,
I tried to model the pk profiles of a drug and its major metabolite in plasma and urine after single oral dose of 30mg. I get the following message corresponding to urine compartment event: SPECIFIED COMPARTMENT MAY NOT BE TURNED OFF WITH AN OBSERVATION RECORD
My controle file and a sample of data file likes:
$INPUT ID TIME AMT UVOL DV CMT MDV EVID CALL AGE HIGH WT
$DATA ALL_DATA.txt IGNORE=#
$SUBROUTINES ADVAN6 TRANS1 TOL=4
$MODEL
COMP=DEPOT
COMP=PLASMA ;PARENT IN PLASMA
COMP=METAB ;METABOLITE IN PLASMA
COMP=DEXURIN ;PARENT IN URINE
COMP=DORURIN ;DEXTROR IN URINE
$PK
KA=THETA(1)
V2=THETA(2)*EXP(ETA(1))
CLP=THETA(3)*EXP(ETA(2)) ;RENAL CL FOR PARENT
CLB=THETA(4) ;METABOLIC CL FOR METABOLIC
CLMR=THETA(5) ;RENAL CL FOR METABOLITE
CLMNR=THETA(6) ;EXTR RENAL CLEARANCE FOR METABOLITE
ALAG1=THETA(7)
V3=1
K23=CLB/V2
K24=CLP/V2
K35=CLMR/V3
K36=CLMNR/V3
S2=V2
S3=V3
S4=UVOL
S5=UVOL
$ERROR
DEL=0
IF(F.EQ.0) DEL=0.0001
W=F
IPRED=F
IRES=DV-IPRED
IWRES=IRES/(W+DEL)
Y=F*EXP(EPS(1))+EPS(2)
$DES
DADT(1)=-KA*A(1)
DADT(2)=KA*A(1)-K24*A(2)-K23*A(2)
DADT(3)=K23*A(2)-K35*A(3)-K36*A(3)
DADT(4)=K24*A(2)
DADT(5)=K35*A(3)
$THETA
(0.01,0.8,6) ;KA
(0.01,43,1000);V2
(0.0001,20,190);CLP
(0.01,15,90);CLB
(0.0001,5,90);CLMR
(0.0001,5,90);CLMR
(0.01,0.2,6) ;ALAG1
$OMEGA
0.05 0.05
$SIGMA
0.2 0.1
$EST POSTHOC PRINT=5 NOABORT MAXEVAL=9999
#ID TIME AMT UVOL DV CMT MDV EVID CALL
2 0.000 30000 0 0 1 1 1 2
2 0.000 0 0 0.000 2 1 0 2
2 0.000 0 0 0.000 3 1 0 2
2 0.171 0 0 0.000 4 1 2 2
2 0.171 0 0 0.000 5 1 2 2
2 2.000 0 0 5.352 2 0 0 2
2 2.000 0 0 5.352 3 0 0 2
2 2.001 0 93.1 880.400 -5 0 0 2
2 2.001 0 93.1 18.215 -4 0 0 2
2 2.002 0 0 0.000 4 1 2 2
2 2.002 0 0 0.000 5 1 2 2
2 3.150 0 0 0.000 2 1 0 2
2 3.150 0 0 0.000 3 1 0 2
2 3.950 0 133.6 962.533 -5 0 0 2
2 3.950 0 133.6 27.697 -4 0 0 2
2 3.951 0 0 0.000 4 1 2 2
2 3.951 0 0 0.000 5 1 2 2
2 6.000 0 0 1.952 2 0 0 2
2 6.000 0 0 1.952 3 0 0 2
2 6.001 0 267.6 289.962 -5 0 0 2
2 6.001 0 267.6 10.200 -4 0 0 2
Thanks in advance for your response.
khaled
Modelling plasma and urine data of a parent and metabolite
Hello Khaled,
Try separating the data rows where you have observations and turning the
compartment of into two different rows
one for the observation i.e with the CMT column positive and another row
negative to turn the compartment off with apropriate EVID and MDV values
Observation + turning off compartment :
#ID TIME AMT UVOL DV CMT MDV EVID CALL
.
.
.
2 2.001 0 93.1 880.400 -5 0 0 2
Replace to
2 2.001 0 93.1 880.400 5 0 0 2
2 2.001 0 93.1 . -5 0 2 2
A good reference to look at is:
Tunblad K, Hammarlund-Udenaes M, Jonsson EN.
An integrated model for the analysis of pharmacokinetic data from microdialysis
experiments.
Pharm Res. 2004 Sep;21(9):1698-707.
Regards,
Samer Mouksassi
Quoted reply history
-----Original Message-----
From: [EMAIL PROTECTED] on behalf of Khaled Mohammed Abduljalil
Sent: Mon 12/11/2007 08:58
To: [email protected]
Subject: [NMusers] Modelling plasma and urine data of a parent and metabolite
Dear nmusers-team,
I tried to model the pk profiles of a drug and its major
metabolite in plasma and urine after single oral dose of
30mg.
I get the following message corresponding to urine
compartment event:
SPECIFIED COMPARTMENT MAY NOT BE TURNED OFF WITH AN
OBSERVATION RECORD
My controle file and a sample of data file likes:
$INPUT ID TIME AMT UVOL DV CMT MDV EVID CALL AGE HIGH WT
$DATA ALL_DATA.txt IGNORE=#
$SUBROUTINES ADVAN6 TRANS1 TOL=4
$MODEL
COMP=DEPOT
COMP=PLASMA ;PARENT IN PLASMA
COMP=METAB ;METABOLITE IN PLASMA
COMP=DEXURIN ;PARENT IN URINE
COMP=DORURIN ;DEXTROR IN URINE
$PK
KA=THETA(1)
V2=THETA(2)*EXP(ETA(1))
CLP=THETA(3)*EXP(ETA(2)) ;RENAL CL FOR PARENT
CLB=THETA(4) ;METABOLIC CL FOR METABOLIC
CLMR=THETA(5) ;RENAL CL FOR METABOLITE
CLMNR=THETA(6) ;EXTR RENAL CLEARANCE FOR
METABOLITE
ALAG1=THETA(7)
V3=1
K23=CLB/V2
K24=CLP/V2
K35=CLMR/V3
K36=CLMNR/V3
S2=V2
S3=V3
S4=UVOL
S5=UVOL
$ERROR
DEL=0
IF(F.EQ.0) DEL=0.0001
W=F
IPRED=F
IRES=DV-IPRED
IWRES=IRES/(W+DEL)
Y=F*EXP(EPS(1))+EPS(2)
$DES
DADT(1)=-KA*A(1)
DADT(2)=KA*A(1)-K24*A(2)-K23*A(2)
DADT(3)=K23*A(2)-K35*A(3)-K36*A(3)
DADT(4)=K24*A(2)
DADT(5)=K35*A(3)
$THETA
(0.01,0.8,6) ;KA
(0.01,43,1000);V2
(0.0001,20,190);CLP
(0.01,15,90);CLB
(0.0001,5,90);CLMR
(0.0001,5,90);CLMR
(0.01,0.2,6) ;ALAG1
$OMEGA
0.05 0.05
$SIGMA
0.2 0.1
$EST POSTHOC PRINT=5 NOABORT MAXEVAL=9999
#ID TIME AMT UVOL DV CMT MDV EVID CALL
2 0.000 30000 0 0 1 1 1 2
2 0.000 0 0 0.000 2 1 0 2
2 0.000 0 0 0.000 3 1 0 2
2 0.171 0 0 0.000 4 1 2 2
2 0.171 0 0 0.000 5 1 2 2
2 2.000 0 0 5.352 2 0 0 2
2 2.000 0 0 5.352 3 0 0 2
2 2.001 0 93.1 880.400 -5 0 0 2
2 2.001 0 93.1 18.215 -4 0 0 2
2 2.002 0 0 0.000 4 1 2 2
2 2.002 0 0 0.000 5 1 2 2
2 3.150 0 0 0.000 2 1 0 2
2 3.150 0 0 0.000 3 1 0 2
2 3.950 0 133.6 962.533 -5 0 0 2
2 3.950 0 133.6 27.697 -4 0 0 2
2 3.951 0 0 0.000 4 1 2 2
2 3.951 0 0 0.000 5 1 2 2
2 6.000 0 0 1.952 2 0 0 2
2 6.000 0 0 1.952 3 0 0 2
2 6.001 0 267.6 289.962 -5 0 0 2
2 6.001 0 267.6 10.200 -4 0 0 2
Thanks in advance for your response.
khaled