Re: simulated negative concentration

From:Nick Holford Subject:Re: [NMusers] simulated negative concentration Date: Fri, 14 Feb 2003 13:28:24 +1300 Here is an example showing how to truncate distributions for both residual error or parameter variability: $PROB THEOPHYLLINE PHARMACODYNAMICS $DATA ..\..\theopd.dat IGNORE # $INPUT ID TIME THEO AGE WT GEND RACE DIAG DV $SIM (20000625 NORMAL NEW) SUBPROBLEMS=2 $ESTIM PRINT=0 $THETA (0,150.,) ; E0 $THETA (0,200.,) ; EMAX $THETA (.001,10,) ; EC50 $OMEGA 0.5 ; CVE0 $OMEGA 0.5 ; CVEMAX $OMEGA 0.5 ; CVEC50 $SIGMA 100 ; SD 1 $PRED E0=E0*EXP(CVE0) EMAX=EMAX*EXP(CVEMAX) EC50=EC50*EXP(CVEC50) IF (ICALL.EQ.4) THEN ; simulation TRUNC=3.27 ; Z 2tailed alpha=0.01 i.e. include 99.9% TVE0=E0 E0=TVE0*EXP(CVE0) LNMU=LOG(TVE0) DLTA=TRUNC*0.717 ; MUST BE 3.27*SQRT(CVE0)! L0=EXP(LNMU-DLTA) H0=EXP(LNMU+DLTA) TVEMAX=EMAX EM=TVEMAX*EXP(CVEMAX) LNMU=LOG(TVEMAX) DLTA=TRUNC*0.717 ; MUST BE 3.27*SQRT(CVEMAX)! LM=EXP(LNMU-DLTA) HM=EXP(LNMU+DLTA) TVEC50=EC50 C5=TVEC50*EXP(CVEC50) LNMU=LOG(TVEC50) DLTA=TRUNC*0.717 ; MUST BE 3.27*SQRT(CVEC50)! L5=EXP(LNMU-DLTA) H5=EXP(LNMU+DLTA) DOWHILE(E0.LT.L0.OR.E0.GT.H0.OR.EM.LT.LM.OR.EM.GT.HM.OR.C5.LT.L5.OR.C5.GT.H5) CALL SIMETA(ETA) EMAX=TVEMAX*EXP(CVEMAX) E0=TVE0*EXP(CVE0) EC50=TVEC50*EXP(CVEC50) ENDDO ENDIF EFFECT=E0 + EM*THEO/(THEO+C5) Y = EFFECT + SD IF (ICALL.EQ.4) THEN ; simulation DOWHILE (Y.LT.0) CALL SIMEPS(EPS) Y=EFFECT + SD ENDDO ENDIF $TABLE ID TIME THEO AGE WT GEND RACE DIAG E0 EM C5 Y NOPRINT ONEHEADER FILE=theopd.fit -- Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/