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: [EMAIL PROTECTED] 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
