Unix to Windows Model Translation / PK Comp Initialization
Dear NONMEM Users,
We have recently run into a rather puzzling problem with a PK/PD model and
are hoping one of the NONMEM experts in the community can provide some
insight. The model was originally developed, and ran well, using a
previously used Unix-based version of NONMEM. However, when we attempted
to re-implement the model with our current, windows-based NONMEM VI, the
model would not run, giving a numerical difficulties error. The bones of
the model are provided below:
$MODEL NCOMP=5
COMP(DEPOT,DEFDOSE)
COMP(CENTRAL)
COMP(PD1)
COMP(PD2)
COMP(PD3,DEFOBS)
$PK
"FIRST
" COMMON /PRCOMG/ IDUM1,IDUM2,IMAX,IDUM4,IDUM5
" INTEGER IDUM1,IDUM2,IMAX,IDUM4,IDUM5
" IMAX=1000000
KA1=KAIN
GAMA1=GAMA
ALAG1=LAGI
V=VIND
CL=CLIN
KAM=KAMI
WB=(1-EXP((-(KA1*TIME)**GAMA1)))*KAM
K20=CL/V
S2=V/1000
BETA=0.00000003
PROD=1.736
V0=VIN0
TD=0.0001
DELT=THETA(1)*EXP(ETA(1))
CV=THETA(2)*EXP(ETA(2))
IC50=THETA(3)*EXP(ETA(3))
HG=THETA(4)*EXP(ETA(4))
T0=(DELT*CV)/(BETA*PROD)
SYN=T0*(TD+(BETA*V0))
F3=T0
F4=(CV*V0)/PROD
F5=V0
$DES
DADT(1)=-WB*A(1)
DADT(2)=WB*A(1)-K20*A(2)
C2=A(2)*1000/V
EFF=(C2**HG/(IC50**HG+C2**HG))
DADT(3)=SYN-A(3)*TD-BETA*A(3)*A(5)
DADT(4)=BETA*A(3)*A(5)-DELT*A(4)
DADT(5)=(1-EFF)*PROD*A(4)-CV*A(5)
The PK parameters are fixed in the model. In order to get the model to
run with our current version of NONMEM, we had to initialize the CENTRAL
compartment with a nominal value (i.e. 1). This was done by modifying the
data set to contain AMT=1 for CMT=2 at TIME=0 for each subject. The
results obtained following this modification are in agreement with those
obtained previously with the original model run in Unix.
Has anyone run into a similar situation when running Unix-developed models
in a windows environment? Has anyone ever encountered a situation where
it was necessary to initialize a PK compartment?
Any insight into this problem would be greatly appreciated.
Regards,
Josh