RE: Simulation problems
From: Toufigh Gordi - tgordi@buffalo.edu
Subject: RE: [NMusers] Simulation problems
Date: 2/5/2004 9:52 AM
Dear Leonid,
After pushing the send button yesterday, I realized that the model, as
presented, works. What doesn't work is if you add: *EXP(ETA(x)) to BASE,
IMAX, and IC50, respectively, where x would be 4, 5, or 6.
I have now done as you suggested and the full model I try to simulate
is given below. It works now, with or without a lower limit on DEN. It
seems that the problem was created by:
CONC=F
Once this line was gone, everything works.
Thanks for the advice.
Toufigh
$PROB ALL DOSES
; 2-COMP
$INPUT ID AMT DATE=DROP TIME DV EVID CMT PKPD
$DATA scpkpdsim.csv IGNORE=#
$SUBROUTINE ADVAN9 TRANS1 TOL=5
$MODEL NCOMP=3
COMP=(SC DEFDOSE)
COMP=CENT
COMP=PERIPH
$PK
VM=THETA(1)*EXP(ETA(1))
KM=THETA(2)
V1=THETA(3)*EXP(ETA(2))
Q=THETA(4)
V2=THETA(5)*EXP(ETA(3))
S2=V1
BASE=THETA(6)*EXP(ETA(4))
IMAX=THETA(7)*EXP(ETA(5))
IC50=THETA(8)*EXP(ETA(6))
KA=THETA(9)
F1=0.6
$DES
CON=A(2)/V1
DADT(1)=-KA*A(1)
DADT(2)=KA*A(1)-A(2)*(VM/(KM+CON))/V1-A(2)*Q/V1+A(3)*Q/V2
DADT(3)=A(2)*Q/V1-A(3)*Q/V2
$ERROR
CONC=A(2)/V1
; CONC=F
DEN=(IC50+CONC)
; IF(DEN.LT.0.00001) DEN=0.00001
LAM=BASE-(IMAX*CONC/DEN)
IF (PKPD.EQ.2) THEN
Y=LAM
ELSE
Y=CONC+EPS(1)
ENDIF
$THETA (7.98 FIXED) ;1 VM
$THETA (11.1 FIXED) ;2 KM
$THETA (41.9 FIXED) ;3 V1
$THETA (0.395 FIXED) ;4 Q
$THETA (39.2 FIXED) ;5 V2
$THETA (54.8 FIXED) ;6 BASE
$THETA (53.7 FIXED) ;7 IMAX
$THETA (0.579 FIXED) ;8 IC50
$THETA (0.1 FIXED) ;9 KA
$OMEGA 0.0791 FIX ;1 IIV VM
$OMEGA 0.0181 FIX ;2 IIV V1
$OMEGA 0.0918 FIX ;3 IIV V2
$OMEGA 0.00328 FIX ;4 IIV BASE
$OMEGA 0.00424 FIX ;5 IIV IMAX
$OMEGA 0.888 FIX ;6 IIV IC50
$SIGMA 0 FIX ;4 ADD ERROR PK
$SIMULATION (20031840) ONLYSIM
$TABLE ID TIME CONC LAM Y PKPD CMT NOPRINT ONEHEADER FILE=SDTAB201
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