bug/feature in $AES
Hi,
Carl Kirkpatrick and I have been trying to use $AES to compute initial values
for use with $DES.
We can get $AES to produce the correct equilibrium values at times after time=0
but cannot access these values at time=0 or at time=0.001. Because the
equilibrium (i.e. initial condition) values are not available at time=0 we
cannot use the NMVI method for initalizing the amounts in the compartments
using A_0(1)=GBASE and A_0(2)=IBASE.
We have inserted dosing records using the old NMV bioavailability trick to try
and initialize the compartments at time=0.002. This almost gets the correct
solution at time=0.002 in both compartments.
Can anyone explain why the algebraic equation results are not available at
time=0 and time=0.001?
Nick and Carl
--- table file output ----- GLU=A(1) INS=A(2)
ID TIME AMT CMT F1 F2 GBASE GLU IBASE INS
1 0 0 1 0 0 0 0 0 0
1 0 0 2 0 0 0 0 0 0
1 0.001 0 1 0 0 0 0.0009 0 0.0024
1 0.002 1 1 187.14 527.49 4.6785 4.6805 13.187 0.0049
1 0.002 1 2 187.14 527.49 4.6785 4.6805 13.187 13.192
1 100 0 1 0 0 4.6785 4.6785 13.187 13.187
1 100 0 2 0 0 4.6785 4.6785 13.187 13.187
---- Control stream --------
$PROB GLUCOSE AND INSULIN INITIAL VALUE
$DATA test.dat
$INPUT ID TIME CMT AMT DV
$SIM (200070927) ONLYSIM NSUB=1
$THETA
40 ; POP_RGLU MMOL/H/70KG
40 ; POP_VGLU L/70KG
4 ; POP_CLGLU L/H/70KG
1 ; POP_EMXGLU
10 ; POP_C50GLU MMOL/L
100 ; POP_RINS NMOL/H/70KG
40 ; POP_VINS L/70KG
10 ; POP_CLINS L/H/70KG
2 ; POP_EMXINS
10 ; POP_C50INS NMOL/L
$OMEGA
0 FIX ;PPV_RGLU
0 FIX ;PPV_RINS
$SIGMA
0.1 ;G_EXP_RUV
1 ;G_ADD_RUV
0.1 ;I_EXP_RUV
1 ;I_ADD_RUV
$SUBR ADVAN9 TOL=3
$MODEL
COMP (GLUCOSE)
COMP (INSULIN)
COMP (GLU EQUILIBRIUM)
COMP (INS EQUILIBRIUM)
$PK
"FIRST
" COMMON/PRCOMG/IDUM1,IDUM2,IMAX
" INTEGER IDUM1,IDUM2,IMAX
" IMAX=1000000
; GLUCOSE
RGLU=THETA(1)*EXP(ETA(1))
VGLU=THETA(2)
CLGLU=THETA(3)
EMXGLU=THETA(4)
C50GLU=THETA(5)
;INSULIN
RINS=THETA(6)*EXP(ETA(2))
VINS=THETA(7)
CLINS=THETA(8)
EMXINS=THETA(9)
C50INS=THETA(10)
GBASE=A(3)/VGLU ; GLUCOSE INITIAL
IBASE=A(4)/VINS ; INSULIN INITIAL
IF (AMT.EQ.1) THEN
F1=GBASE
F2=IBASE
ELSE
F1=0
F2=0
ENDIF
S1=VGLU
S2=VINS
$AESINITIAL
INIT=0
A(3)=5 ; MMOL/L
A(4)=10 ; NMOL/L
$AES
EGLU=A(3)/VGLU
EINS=A(4)/VINS
EGEFF=EMXGLU*EGLU/(C50GLU+EGLU)
EIEFF=EMXINS*EINS/(C50INS+EINS)
E(3)=RGLU - CLGLU*(1+EIEFF)*EGLU ; GLUCOSE EQUILIBRIUM
E(4)=RINS*(1+EGEFF) - CLINS*EINS ; INSULIN EQUILIBRIUM
$DES
DGLU=A(1)/VGLU
DINS=A(2)/VINS
DGEFF=EMXGLU*DGLU/(C50GLU+DGLU)
DIEFF=EMXINS*DINS/(C50INS+DINS)
DADT(1)=RGLU - CLGLU*(1+DIEFF)*DGLU
DADT(2)=RINS*(1+DGEFF)- CLINS*DINS
$ERROR
GLU=A(1)/VGLU
INS=A(2)/VINS
IF (CMT.EQ.1)THEN
Y=GLU*(1+ERR(1))+ERR(2)
ENDIF
IF (CMT.EQ.2)THEN
Y=INS*(1+ERR(3))+ERR(4)
ENDIF
$TABLE ID TIME AMT CMT F1 F2 GBASE GLU IBASE INS
NOAPPEND ONEHEADER NOPRINT FILE=test.fit
---- test.dat --------------------
#id,time,cmt,amount,dv
1,0,1,.,.
1,0,2,.,.
1,0.001,1,.,.
1,0.002,1,1,.
1,0.002,2,1,.
1,100,1,.,.
1,100,2,.,.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford