Dear NMusers, I'm a NM beginner modeling for a monoclonal antibody. Below is 12 subjects's individual predicted plot , it seems that nonlinear elimination (Michaelis-Menten) model can fit the data well. However, when running the control stream (two compartment models with linear and non-linear elimination), the resulting Q THETA SE% and OMEGA SE% are quite large even thought successful minimization.From the Correlation Matrix , I find that THETA (1) (VMAX) and THETA(2) (KM)are highly correlated (9.67E-01). Another problem is the .fit file can't be produced.
I have tried various error models and initial estimations, however, none had better improvement and often got error message (error 134 or parameter estimate is near its boundary). Does re-parameterization helpful ? or need to change to other models? Any suggestions for solving the problems are highly appreciated. =================================================================== THETA: VMAX KM V1 V2 Q ETA: BSVV1 ERR: ERR run2.3.lst -167.989 eval=237 sig=+3.5 sub=12 obs=100 CCIL=YNYN NVI2.0 PV2.0 THETA = 7.35 59.6 3.68 0.87 0.0538 ETASD = 0.0676018 ERRSD = 0.25632 THETA:se% = 8.4 22.5 5.8 32.3 80.3 OMEGA:se% = 194.5 SIGMA:se% = 20.1 MINIMIZATION SUCCESSFUL P VAL.: 0.10E+01 @ Ttot 0:44.28 Test 0:44.28 Tcov 0 Ttcl 0:0.44 $PROBLEM BASE MODEL $DATA ..\PKDATA.CSV IGNORE=# $INPUT ID TIME AMT NDV=DROP LNDV=DV EVID MDV CMT BW AGE DOSE RATE DUR $SUBROUTINE ADVAN8 TOL=6 $MODEL COMP=(CENTRAL, DEFOBS, DEFDOSE) COMP=(PERIPH) $PK TVVMAX=THETA(1) VMAX=TVVMAX KM=THETA(2) TVV1=THETA(3) V1=TVV1*EXP(ETA(1)) TVV2=THETA(4) V2=TVV2 Q=THETA(5) S1=V1 D1=DUR $DES C1=A(1)/V1 C2=A(2)/V2 DADT(1)=-VMAX*C1/(KM+C1)-(Q*C1)+(Q*C2) DADT(2)=(Q*C1)-(Q*C2) $ERROR IPRED=LOG(F) IRES=DV-IPRED IWRES=IRES/IPRED Y=IPRED+ERR(1) $THETA (0.1, 7, ) ;VMAX (1, 57,300) ;KM (0, 4, 6) ;V1 (0, 1, 6) ;V2 (0.001, 0.003, ) ;Q $OMEGA 0.001 ; BSVV1 $SIGMA 0.5 ;ERR $ESTIMATION METHOD=1 INTERACTION MAXEVALS=9999 POSTHOC NOABORT NSIG=3 $COVARIANCE UNCONDITIONAL SLOW PRINT=E $TABLE ID TIME DV IPRED VMAX KM V1 V2 Q ETA1 NOPRINT ONEHEADER FILE= run2.3.fit $TABLE ID TIME AMT IPRED IWRES NOPRINT ONEHEADER FILE=sdtab1 $TABLE ID VMAX KM V1 V2 Q ETA1 NOPRINT ONEHEADER FILE=patab1 $TABLE ID BW AGE NOPRINT ONEHEADER FILE=cotab1
