log transformed data and multi compartment PK

From: "ZDROJEWSKI,IMMO" zdrojew@ufl.edu Subject: [NMusers] log transformed data and multi compartment PK Date: Tue, 26 Jul 2005 17:17:57 -0400 (EDT) Dear NONMEM users, I was trying to model the PK of a drug that shows high variablility in the data. In order to improve the speed of NONMEM and improve the high variability I tried to log tranform the data. I can make it work, modeling one compartment only, however, since I have data for the metabolite, I want to model praent drug and metabolite. When I start the Nonmem run, I get an error message saying: run-time error M6202: math - log: SING error I figure that it might have something to do with the log function, but nothing worked so far to fix it. Does anybody have an idea what I could cahnge in the attached code? Thanks a lot in advance Immo ----------------------- $SUBROUTINE ADVAN8 TOL=5 $MODEL ;SPECIFIES WITH MODEL FROM PREDPP IS USED TO FIT THE DATA. NCOMPARTMENTS=3 COMP = SVA COMP = SV COMP = SVAP $PK ;$PK ASSIGNS THETAS TO FIXED EFFECT PARAMETERS AND SPECIFIES THE RANDOM EFFECT MODEL ;E.G ADDITIVE, PROPORTIONAL, EXPONENTIAL TVK1=THETA(1) K12=TVK1*EXP(ETA(1)) TVK2=THETA(2) K21=TVK2*EXP(ETA(2)) TVKE=THETA(3) KE=TVKE*EXP(ETA(3)) TVVD=THETA(4) VD=TVVD*EXP(ETA(4)) TVKL=THETA(5) KL=TVKL*EXP(ETA(5)) TVKA=THETA(6) KA=TVKA*EXP(ETA(6)) TVKX=THETA(7) KX=TVKX*EXP(ETA(7)) TVSV=THETA(8) SV=TVSV*EXP(ETA(8)) ;THETA IS THE ESTIMATED POPULATION VALUE, EXPONENTIAL BETWEEN SUBJECT VARIABILITY IS USED HERE, ;ETA IS THE BETWEEN SUBJECT VARIABILITY S1=VD/1000 S2=SV/1000 ;S=SCALING FACTOR TO ADJUST FOR THE UNITS, DOSE= MG CONC = NG/ML SCALING FACTOR = 1000 $ERROR (OBSERVATION ONLY) Q1=0 IF(CMT.EQ.1) Q1=1 Y1=LOG(F)+ERR(1) Q2=0 IF(CMT.EQ.2) Q2=1 Y2=LOG(F)+ERR(2) Y=Q1*Y1+Q2*Y2 IPRED=LOG(F) $DES DADT(1)= -KE*A(1)-K12*A(1)+K21*A(3)-KA*A(1)+KL*A(2) DADT(2)= KA*A(1)-KL*A(2)-KX*A(2) DADT(3)= K12*A(1)-K21*A(3) $THETA (0,2.7) ;(0,2,10) THETAK12 (0,0.27) ;(0,0.5,10) THETA K21 (0,4.5);(0,0.83,10)NTHEATKE (0,8) ;(0,210) THETAVD (0,0.09) ;K LACTONE TO ACID (0,0.16) ;K ACID TO LACTONE (0,1.5) ;KX ELIMINATION FOR SV (0,25.7) ; VDSV ESTIMATE $OMEGA 0.09 0.09 0.01 0.09 0.09 0.09 0.09 0.09 $SIGMA 1 1 $ESTIMATION METH=0 MAXEVAL=9999 PRINT=5 MSFO=002NM20LOG.MSF ;SIGDIG=2 $COVARIANCE $TABLE ID TIME TVK1 K12 ETA1 TVK2 K21 ETA2 TVKE KE ETA3 TVVD VD ETA4 TVKL KL ETA5 TVKA KA ETA6 TVKX KX ETA7 TVSV SV ETA8 ID CMT ;IPRED NOPRINT FILE=002NM20LOG.FIT X ID CMT TIME CONC AMT RATE MDV 0 1 1 0 . 1.301029996 1.602059991 1 0 1 2 0 . 0 0 1 0 1 1 0.25 2.702266783 0 0 0 0 1 2 0.25 -0.086186148 0 0 0 0 1 1 0.5 2.837481114 0 0 0 0 1 2 0.5 -0.283996656 0 0 0 0 1 1 0.67 2.109659527 0 0 0 0 1 2 0.67 -0.427128398 0 0 0 0 1 1 0.83 1.893040112 0 0 0 0 1 2 0.83 -0.368556231 0 0 0 0 1 1 1 1.740094134 0 0 0 0 1 2 1 -0.242603971 0 0 0 0 1 1 1.5 1.544626064 0 0 0 0 1 2 1.5 -0.240332155 0 0 0 -- Immo Zdrojewski, Pharmacist Graduate Student @ Pharmaceutics: (352)-846-2584 @ Nursing: (352)-273-6513 e-mail: zdrojew@ufl.edu