[NMusers] 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
Received on Fri Dec 07 2007 - 14:27:39 EST