NONMEM Users Network Archive

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No. of parameters estimated

From: navin goyal <navin1180>
Date: Fri, 17 Aug 2007 12:50:42 -0400

Dear NM Users,
I have been trying to do a POPPK run using nonmem VI.
The part of my control stream is pasted 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))
TVV2=THETA(3);vol of dist of drug
V2=TVV2*EXP(ETA(3))
K20=TVCL/TVV2
K23=(THETA(6)+THETA(4))+EXP(ETA(4));
K32=THETA(5)+EXP(ETA(5))
TVK12=THETA(6);Abso constant
K12=TVK12+EXP(ETA(6))
S2=V2; OUTPUT IN ng/ml and dose in micrograms

$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);F
(46 FIXED);CL
(0,25,200);V2
(0.01,0.1,10);K23
(0.01,0.1,10);K32
(0.01,0.1,2);K12

$OMEGA
$SIGMA

$ESTIMATION METHOD=1 SIGDIGITS=5 INTERACTION MAXEVAL=9999 PRINT=10 POSTHOC
$COV MATRIX=S

The model is very sensitive to the initial estimates and when I bootstrapped
the model about half of the runs failed to minimize. Also the variability
asssociated with parameter estimates is very high. The data is from 11
subjects and has high variability. I tried various models, including using
FO Method. Am I trying to estimate more parameters (like KA, F, Vd, K23,
K32) with very limited information ? or is it model misspecification...
Or should I fix other parameters like Vd from IV data. (here I have fixed
Cl from IV data...when I dont not fix CL , the nonmem estimates very small
values of CL ... in decimals)

Any input is appreciated.........
Thanks

--
--Navin

Received on Fri Aug 17 2007 - 12:50:42 EDT

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