[NMusers] RE: [NMusers] Differences with ADVAN3 TRANS1 and ADVAN3 TRANS4

The way the random terms are entered between the two models will affect your
results,

 

Eg. Etas on K's versus etas on CL,V

 

  _____

From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On
Behalf Of Paul Collier
Sent: Thursday, May 01, 2008 10:30 AM
To: nmusers_at_globomaxnm.com
Subject: [NMusers] Differences with ADVAN3 TRANS1 and ADVAN3 TRANS4

 

Please could someone explain why I get very different results when using
ADVAN3 TRANS1 to model a data set compared with using ADVAN3 TRANS4? Using
the rate constants obtained with TRANS1 for a two compartment model to
compute clearance and volume terms gives different values to those obtained
with TRANS4. I have tried using various initial estimates for the runs but
this has not solved the problem. I have listed typical outputs from Wings
for NONMEM below for each of the two ways of parameterising the two
compartment model. The objective function is considerably smaller with
TRANS1 ( -580 compared with -533).

 

Thanks,

 

Paul

 

 

Paul S. Collier

School of Pharmacy

Queen's University Belfast

Email: p.collier_at_qub.ac.uk

 

 

Using ADVAN3 TRANS1

THETA: ELIMINATION RATE RATE VOLUME

ETA: OMEGA

ERR: SIGMA

run209.lst -580.598 eval=209 sig=+3.4 sub=43 obs=184
CCIL=YNYN NVI1.1 PV1.0

THETA = 0.477 0.357 0.255 7.44

ETASD = 0.806846 0.000457165 0.00758947 1.40357

ERRSD = 0.242693

THETA:se% = 22.9 15.9 23.9 30.2

OMEGA:se% = 26.3 10287.1 559.0 27.7

SIGMA:se% = 23.4

 

MINIMIZATION SUCCESSFUL

 

P VAL.: 0.75E+00 0.17E+00 0.46E+00 0.88E+00

 

 MIDAZOLAM 2-COMP RATES MODEL ADDITIVE ERROR

   user 0:21.95 real 0:21.95 tcl 0:0.42

 

$PROBLEM MIDAZOLAM 2-COMP RATES MODEL EXPONENTIAL ERROR

$INPUT ID TIME DAT1=DROP AGE DOSE=AMT RATE DV WT BUC MDV GEN

$DATA ..\MIDAZOLAM.CSV

$SUBROUTINES ADVAN3 TRANS1

 

$PK

CALLFL=1

 

TVK=THETA(1)

K=TVK*EXP(ETA(1))

 

TVK12=THETA(2)

K12=TVK12*EXP(ETA(2))

 

TVK21=THETA(3)

K21=TVK21*EXP(ETA(3))

 

TVV=THETA(4)

V=TVV*EXP(ETA(4))

 

S1=V

 

$ERROR

 

IPRED=F

IRES=DV-IPRED

W=F

IWRES=IRES/W

 

Y=F*(1+ERR(1))

 

 

 

$THETA (0,0.5)

 

$THETA (0,0.5)

 

$THETA (0,0.5)

 

$THETA (0,10)

 

$OMEGA 0.01 0.01 0.01 0.01

 

$SIGMA 0.4

 

$ESTIMATION MAXEVAL=9999 PRINT=2 METHOD=CONDITIONAL INTERACTION

 

 

Using ADVAN3 TRANS4

THETA: CLEARANCE VOLUME1 INTERCOMPARTMENTAL CLEARANCE
VOLUME2

ETA: OMEGA

ERR: SIGMA

run213.lst -533.475 eval=380 sig=+4.5 sub=43 obs=184
CCIL=YNYN NVI1.1 PV1.0

THETA = 3.19 0.209 9.87 12

ETASD = 1.25698 0.000467974 0.00130767 0.849706

ERRSD = 0.283019

THETA:se% = 20.4 85.2 49.2 31.2

OMEGA:se% = 15.5 20821.9 6432.7 43.6

SIGMA:se% = 24.5

 

MINIMIZATION SUCCESSFUL

 

P VAL.: 0.97E+00 0.93E+00 0.80E+00 0.31E+00

 

   user 0:33.95 real 0:33.95 tcl 0:0.52

 

$PROBLEM MIDAZOLAM 2-COMP CLEARANCE MODEL

$INPUT ID TIME DAT1=DROP AGE DOSE=AMT RATE DV WT BUC MDV GEN

$DATA ..\MIDAZOLAM.CSV

$SUBROUTINES ADVAN3 TRANS4

 

$PK

CALLFL=-1

 

TVCL=THETA(1)

CL=TVCL*EXP(ETA(1))

 

TVV1=THETA(2)

V1=TVV1*EXP(ETA(2))

 

TVQ=THETA(3)

Q=TVQ*EXP(ETA(3))

 

TVV2=THETA(4)

V2=TVV2*EXP(ETA(4))

 

S1=V1

 

 

 

$ERROR

 

IPRED=F

IRES=DV-IPRED

W=F

IWRES=IRES/F

 

Y=F*(1+ERR(1))

 

 

 

$THETA (0,3)

 

$THETA (0,0.1)

 

$THETA (0,1)

 

$THETA (0,10)

 

 

$OMEGA 0.04 0.04 0.04 0.04

 

$SIGMA 0.4

 

$ESTIMATION MAXEVAL=9999 PRINT=2 METHOD=CONDITIONAL INTERACTION

 

$COVR PRINT=E

 

 


  _____

No viruses found in this incoming message
Scanned by iolo AntiVirus 1.5.3.5
http://www.iolo.com <http://www.iolo.com/iav/iavpop3>


_______________________________________
No viruses found in this outgoing message
Scanned by iolo AntiVirus 1.5.3.5
http://www.iolo.com


Received on Thu May 01 2008 - 10:48:48 EDT