INITIAL OBJ FUNCTION ERROR

From: "nelamangala nagaraja" <nvnagaraj@hotmail.com> Subject: INITIAL OBJ FUNCTION ERROR Date: Wed, 05 Apr 2000 01:00:15 EDT Dear NM Users, I am fitting a dataset with parent drug (actually a prodrug) and its metabolite, both following a 2-compartment model and present in plasma and CSF. I am using ADVAN6 for modeling. When I started nonmem execution, it was immediately terminated with the following message in the output file: MONITORING OF SEARCH: 0PROGRAM TERMINATED BY OBJ ERROR IN CELS WITH INDIVIDUAL 5 ID= .50000000E+01 WEIGHTED SUM OF "SQUARED" INDIVIDUAL RESIDUALS IS INFINITE MESSAGE ISSUED FROM ESTIMATION STEP AT INITIAL OBJ. FUNCTION EVALUATION The control file is as follows $PROBLEM PRODRUG AND DRUG IN PLASMA AND CSF $INPUT ID TIME AMT DV RATE CMT MDV $DATA MPHSMPPC1.CSV IGNORE=C $SUBROUTINE ADVAN6 TRANS 1 TOL=3 $MODEL COMP=(CENTRAL1) COMP=(PERIPH1) COMP=(CENTRAL2) COMP=(PERIPH2) COMP=(CSF1) COMP=(CSF2) $PK TVCL1 = THETA(1) TVV1 = THETA(2) K12A = THETA(3) K21A = THETA(4) TVCL2 = THETA(5) TVV2 = THETA(6) K34A = THETA(7) K43A = THETA(8) KF = THETA(9) K12B = THETA(10) K21B = THETA(11) K34B = THETA(12) K43B = THETA(13) CL1=TVCL1*EXP(ETA(1)) V1=TVV1*EXP(ETA(2)) CL2=TVCL2*EXP(ETA(3)) V3=TVV2*EXP(ETA(4)) S1=V1 S3=V3 S5=0.125 S6=0.125 K1=CL1/V1 K2=CL2/V3 $DES DADT(1)=-(K1-KF)*A(1)+ K21A*A(2)-K12A*A(1)-K12B*A(1)+K21B*A(5) DADT(2)=-K21A*A(2)+K12A*A(1) DADT(3)=KF*A(1)-K2*A(3)-K34A*A(3)+K43A*A(4)-K34B*A(3)+K43B*A(6) DADT(4)=K34A*A(3)-K43A*A(4) DADT(5)=K12B*A(1)-K21B*A(5) DADT(6)=K34B*A(3)-K43B*A(6) $THETA (0.001, 18) (0.001, 22) (0.0001, 1.5) (0.0001, 0.8) (0.0001, 20) (0.001, 30) (0.001, 1.1) (0.001, 1.2) (0.0001, 0.45) (0, 0.01) (0, 0.012) (0, 0.015) (0, 0.011) $OMEGA 0.1 ; FOR CL1 0.1 ; FOR V1 0.15; FOR CL2 0.12; FOR V3 $ERROR R1=0 IF (CMT.EQ.1) R1=1 R2=0 IF (CMT.EQ.3) R2=1 R3=0 IF (CMT.EQ.5) R3=1 R4=0 IF (CMT.EQ.6) R4=0 Y1=F+EPS(1) Y2=F+EPS(2) Y3=F+EPS(3) Y4=F+EPS(4) Y=R1*Y1+R2*Y2+R3*Y3+R4*Y4 IPRED=F IRES=DV-IPRED $SIGMA 0.1 0.2 0.01 0.01 $ESTIMATION METHOD=0 MAXEVAL=9999 PRINT=5 $TABLE ID TIME AMT CL1 V1 K12A K21A CL2 V3 K34A K43A KF K12B K21B K34B K43B NOPRINT ONEHEADER FILE=MPHSMPPC1B I tried to use both additive and exponential error models Could you please suggest a solution for this. Thanks Raj N.V. Nagaraja Post Doc Res Assoc Department of Pharmaceutics, University of Florida, Gainesville, FL-32610 Ph: 352-846-3257 Fax: 352-392-4447