problem about enterohepatic circulation model. Thanks!!!!
From: "XIAOHUI WEI" wei.72@osu.edu
Subject: [NMusers] problem about enterohepatic circulation model. Thanks!!!!
Date: Sun, February 13, 2005 10:58 am
Dear NONMEM users,
I adapted an enterohepatic circulation model developed by Luann Phillips to
fit my clinical data for 22 patients.
Thirty minute IV bolus followed by four hours IV infusion has used as dosing
regimen. Gallbladder was turned on by meals at 0, 4.5, 8, 12 hr. However,
I always got the following message as ?MINIMIZATION TERMINATED DUE TO
INFINITE INITIAL VALUE OF OBJ. FUNC. AT INITIAL ESTIMATE.? It seemed the
NONMEM never run a single step. I listed the control stream and first
patient data as follows. I highly appreciate your input and suggestions.
Di Wu
Division of Pharmaceutics
College of Pharmacy
The Ohio State University
Tel: (614) 397-0963
E-mail: diwu88@hotmail.com
$PROB FLAP EHC MODEL
$INPUT C ID TIME AMT RATE DUR DV CMT EVID ADDL II
$DATA ***.csv IGNORE=C
$SUBROUTINES ADVAN6 TRANS1 TOL=5
$MODEL
NCOMPARTMENTS=12
COMP=(GI) ;GI compartment
COMP=(CENTRAL,DEFDOSE,DEFOBS) ;dosing compartment
COMP=(PERI,NODOSE) ;peripherial compartment
COMP=(GB,NODOSE) ;gall bladder
COMP=(GB0ON) ;dummy cmt to turn on GB exit at breakfast
COMP=(GB0OFF) ;dummy cmt to turn off GB exit at
breakfast
COMP=(GB4ON) ;dummy cmt to turn on GB exit at lunch
COMP=(GB4OFF) ;dummy cmt to turn off GB exit at lunch
COMP=(GB8ON) ;dummy cmt to turn on GB exit at dinner
COMP=(GB8OFF) ;dummy cmt to turn off GB exit at dinner
COMP=(GB12ON) ;dummy cmt to turn on GB exit at
post-dinner
COMP=(GB12OFF) ;dummy cmt to turn off GB exit at
post-dinner
$PK
CALLFL=-2
KA=THETA(1)
TVCL=THETA(2)
CL=TVCL*EXP(ETA(1))
TVVC=THETA(3)
V2=TVVC*EXP(ETA(2))
K23=THETA(4)
K32=THETA(5)
K24=THETA(6)
K41=THETA(7)
GBL=THETA(8)
ALAG5=0.0001
ALAG6=ALAG5+GBL
ALAG7=4.5001
ALAG8=ALAG7+GBL
ALAG9=8.0001
ALAG10=ALAG9+GBL
ALAG11=12.0001
ALAG12=ALAG11+GBL
S2=V2
IF(NEWIND.LT.2) THEN
JON=1
JOFF=0
ENDIF
IF(JON.EQ.1) Z=1
IF(JOFF.EQ.1) Z=0
JON=0
JOFF=0
IF(DOSREC(CMT).EQ.5.OR.DOSREC(CMT).EQ.7) JON=1
IF(DOSREC(CMT).EQ.9.OR.DOSREC(CMT).EQ.11) JON=1
IF(DOSREC(CMT).EQ.6.OR.DOSREC(CMT).EQ.8) JOFF=1
IF(DOSREC(CMT).EQ.10.OR.DOSREC(CMT).EQ.12) JOFF=1
$DES
K10=CL/V2
DADT(1)=-KA*A(1)+K41*Z*A(4)
DADT(2)=RATE+KA*A(1)+K32*A(3)-K23*A(2)-K24*A(2)-K10*A(2)
DADT(3)=K23*A(2)-K32*A(3)
DADT(4)=K24*A(2)-K41*Z*A(4)
DADT(5)=0
DADT(6)=0
DADT(7)=0
DADT(8)=0
DADT(9)=0
DADT(10)=0
DADT(11)=0
DADT(12)=0
$ERROR
Y=F*(1+EPS(1))
$THETA
(0,1,) ;KA:theta 1
(0,30,) ;clearance: theta 2
(0,300,) ;Vc:theta 3
(0,0.1,) ;k23:theta 4
(0,0.08,) ;k32:theta 5
(0,0.0001,) ;k24:theta 6
(0,0.01,) ;k41:theta 7
(0,1.5,) ;elapsed time GB exit is 'on' (theta9)
$OMEGA 0 FIXED 0 FIXED
$SIGMA 0.04
$EST MAXEVAL=9999 PRINT=9 SIGDIGITS=3 METHOD=1
;$COV
$SCAT DV VS PRED UNIT
$SCAT (PRED,ID) VS RES
$SCAT (PRED,ID) VS WRES
$TABLE ID TIME AMT DV
C ID TIME AMT RATE DUR DV CMT EVID ADDL II
. 1 0 64.5 129 0.5 . 2 1 0 0
. 1 0 1 . . . 5 1 1 24
. 1 0 1 . . . 6 1 1 24
. 1 0 1 . . . 7 1 1 24
. 1 0 1 . . . 8 1 1 24
. 1 0 1 . . . 9 1 1 24
. 1 0 1 . . . 10 1 1 24
. 1 0 1 . . . 11 1 1 24
. 1 0 1 . . . 12 1 1 24
. 1 0 0 . . 0 2 0 . .
. 1 0.5 64.5 16.125 4 . 2 1 0 0
. 1 0.5 . . . 0.80365 2 0 . .
. 1 4.5 . . . 0.388295 2 0 . .
. 1 6 . . . 0.196346 2 0 . .
. 1 8 . . . 0.121071 2 0 . .
. 1 12 . . . 0.037589 2 0 . .
. 1 18 . . . 0.020977 2 0 . .
. 1 24 . . . 0.016595 2 0 . .
. 1 32 . . . 0.029634 2 0 . .
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