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

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