[NMusers] Differences with ADVAN3 TRANS1 and ADVAN3 TRANS4

Please could someone explain why I get very different results when using AD=
VAN3 TRANS1 to model a data set compared with using ADVAN3 TRANS4? Using th=
e rate constants obtained with TRANS1 for a two compartment model to comput=
e 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 NO=
NMEM below for each of the two ways of parameterising the two compartment m=
odel. 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 VOLU=
ME2

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




Received on Thu May 01 2008 - 10:30:13 EDT