[NMusers] Minimization terminated ?

Dear NM Users,
I am using trying to model some POPPK data in NONMEM vi
Sometimes I get the following message in the output file

MINIMIZATION TERMINATED
 DUE TO ROUNDING ERRORS (ERROR=134)
 NO. OF FUNCTION EVALUATIONS USED: 1103
 NO. OF SIG. DIGITS UNREPORTABLE

But when I change the SIGDIGITS to a lower value the minimization is
successful. What exactly is happening in this case ? Is there something I am
missing out?

what about the parameter estimates obtained in such a run ?

Another question related to this is that when I bootstrap a model in wings
for nonmem WFN, I get few runs with similar message where in it also says
the same message as above ..MINIMIZATION TERMINATED DUE TO ROUNDING ERRORS
(ERROR=134) NO. OF SIG. DIGITS UNREPORTABLE.
This means that I discard these runs from the calculations ?

I have attached the control stream below :

$SUBROUTINE ADVAN6 TRANS1 TOL=3
$MODEL
COMP=(DEPOT,DEFDOSE);
COMP=(CENTRAL);PLASMA
COMP=(PERIPH);PERIPHERAL

$PK
TVF1=THETA(1)
F1=TVF1*EXP(ETA(1))
TVCL=THETA(2)
CL=TVCL*EXP(ETA(2))
TVVC=THETA(3);vol of dist of drug
VC=TVVC*EXP(ETA(3))
TVK20=THETA(4)
K20=TVK20*EXP(ETA(4))
K12=THETA(5)*EXP(ETA(5));Abso constant
K23=THETA(6)*EXP(ETA(6))
K32=THETA(7)*EXP(ETA(7))
CL=K20*VC
SC=VC; OUTPUT IN ng/ml

$ERROR
IPRED=F
IRES=DV-IPRED
DEL=0
IF (IPRED.EQ.0) DEL=1
IWRE=(1-DEL)*IRES/(IPRED+DEL)
Y=F+F*ERR(1);+ERR(2)

$DES
DADT(1)=-K12*A(1)
DADT(2)=K12*A(1)-K20*A(2)-K23*A(2)+K32*A(3)
DADT(3)=K23*A(2)-K32*A(3)

$THETA
(0.1,0.3,0.7);
(75 FIXED);CL
(0,550,1000);VC
(0.02,0.2,2);K20
(7 FIXED);K12
(0.01 ,0.1,10);K23
(0.01,0.1,10);K32

$OMEGA
(0.01);INH
(0.001);CL
(0.01);VC
(0.01);K20
(0.01);K12
(0.01);K23
(0.01);K32

$SIGMA
(0.04);

$ESTIMATION METHOD=1 SIGDIGITS=2 MAXEVAL=9999 PRINT=10 POSTHOC
$COV MATRIX=S

$TABLE ID TIME EVID CMT IPRED IWRE IRES CL VC K20 F1
NOPRINT ONEHEADER FILE=sdtabdoc5
--
--Navin

Received on Thu Jul 19 2007 - 12:02:23 EDT