problem with simulation
From: "kai wu"
Subject: [NMusers] problem with simulation
Date: Tue, November 30, 2004 11:52 am
Dear users,
I am doing a pk-pd simulation with indirect response model to see the inhibition in two PD compartment.
I set up three occasions, for two different doses and baseline respectively.
PK follow 2-comp, and the inhibiton will be quantified as AUC in 24 hrs.
After simulation I found there is something wrong with the simulated concentrations in the second PD compartment.
The baseline AUC is actually much lower than the AUC after dosing, and the starting steady concentration(at 24hr) at baseline
is much lower than the other two dosing occations. The model used in this simulation was also tried by "SCIENTIST"
for single subject and the results were right as supposed. So I am hoping someone can point out where I am doing wrong
in this NONMEM simulation.
The basic code is as followings:
$PROBLEM PKPD
$INPUT ID TIME AMT DV CMT EVID OCC
$DATA ALL1.CSV IGNORE=#
$SUBROUTINES ADVAN6 TRANS1 TOL=5
$MODEL
COMP=(! DEPOT) ;1
COMP=(CENTRAL) ;2
COMP=(PERIPH) ;3
COMP=(CORT);4
COM=(LYM);5
$ABBREVIATED DERIV2=NO
$PK ...
RRBE=935
RRBC=7.8
IF (OCC.EQ.3) RRBC=935
...
$DES
DADT(1)=-KA*A(1)
DADT(2)=KA*A(1)-K10*A(2)
CP=A(2)/S2
EFFC=1-CP*0.12/(EC50+CP*0.12)
DADT(3)=RCORT*EFFC-KE*A(3)
Cort=A(3)/S3
KTC=30000000
KALB=5000
QTC=0.0000007
QALB=0.00055
MW=362.47*(10**6)
CortM=Cort/MW
B1=KTC*QTC+KALB*QALB+1-CortM*KTC
A1=KALB*QALB*KTC+KTC
CORTFM=(-B1+SQRT(B1**2+4*A1*CortM))/(2*A1)
Cortf=CORTFM*MW
UPP=CP*0.12+Cortf*RRBC/RRBE
DOW=EC50CL+CP*0.12+Cortf*RRBC/RRBE
EFFL=1-UPP/DOW
DADT(4)=KIN*EFFL-KOUT*A(4)
...
$SIGMA
(0 FIXED)
(0 FIXED)
(0 FIXED)
...
And the data file is basically set up as
#ID TIME AMT DV CMT EVID OCC
1 0 0 4 0 1
1 0 0 5 0 1
1 24 1000 1 1 1
1 24 0 2 0 1
1 24 0 4 0 1
1 24 0 5 0 1
Thanks in advance!
Kai Wu
Department of Pharmaceutics
University of Florida
Gainesville, Fl
Office phone #: 352-846-2730