NONMEM

From: "Ritu Karwal" Ritu.Karwal@ranbaxy.com Subject: [NMusers] NONMEM Date: Thu, 14 Sep 2006 09:48:21 +0530 Dear nmusers: Can anybody suggest me how to perform optimization of sampling time points in NONMEM or using any other software? I have read somewhere that there is a command $SUPER in NONMEM to perform this. Also, I have got a control stream (which I have got from nmusers previous messages only posted by Ludger Banken) for this but that is not working. Below is that control stream. Also can anybody tell me what RATD, COVA, EVID, SS stands for in this control stream. I have recently started working on population pharmacokinetics and NONMEM so I dont know these words? With regards, Ritu Karwal, M.Sc (Statistics) Research Associate, Metabolism and Pharmacokinetics, Ranbaxy Research Laboratories Limited. $PROB Popkin Dummy Simulation for first starting value of the seed ;This problem is only here to allow the use of the seed (-1) later on $THETA (.1,1.4 ,10) ;Ka 1 $THETA (.1,3.5 ,50) ;CL 2 $THETA (1,20 ,1000) ; V 3 $THETA (1 ,1 ,1 ) ;F 4 $THETA (-2,0.2 ,2) ; CL (Covar) 5 $OMEGA 0.223144 ;kA $OMEGA 0.039221 0.039221 ;CL V $OMEGA .0001 FIXED;F $SIGMA 0.039221 ;ERR Mult $SIGMA 0.005 ;Err Add $SIGMA 1 FIXED; Random time $DATA SLB.nm $INPUT ID TIME AMT DV MDV EVID SS II ADDL RATD COVA $SIMULATION (35436 ) ONLY SUB=1 $SUBROUTINE ADVAN2 TRANS=2 $PK ;This PK block has to be used in all problems below ;Therefore all model must be covered by this model KA = THETA(1) * EXP(ETA(1)) CL = THETA(2) * EXP(ETA(2))*COVA**THETA(5 ) V = THETA(3) * EXP(ETA(3)) F1 = THETA(4) * EXP(ETA(4)) S2=V $ERROR CP=F Y = F * EXP( EPS(1) ) + EPS(2) IF (AMT.GT.0) THEN ATIME=TIME RTIME=TIME LTIME=TIME ENDIF MDV2=MDV IF (TIME.EQ. 101) RTIME=ATIME+1.7320508076 *EXP(0.3339544233 *EPS(3)) IF (TIME.EQ. 102) RTIME=ATIME+23.916521486 *EXP(0.050780836 *EPS(3)) IF (TIME.EQ. 201) RTIME=ATIME+3.4641016151 *EXP(0.0874491407 *EPS(3)) IF (TIME.EQ. 202) RTIME=ATIME+5.4772255751 *EXP(0.055421818 *EPS(3)) IF (TIME.EQ. 203) RTIME=ATIME+7.4833147735 *EXP(0.0405906612 *EPS(3)) IF (RTIME.LE.LTIME) THEN RTIME=LTIME+.01 MDV2=1 ENDIF LTIME=RTIME $SUPER SCOPE=4 ITERATIONS=100 ;This is the big DO Loop around the following Models $PROB Popkin Simulation 1 to generate random Time $THETA (.1,1.4 ,10) ;Ka 1 $THETA (.1,3.5 ,50) ;CL 2 $THETA (1,20 ,1000) ; V 3 $THETA (1 ,1 ,1 ) ;F 4 $THETA (-2,0.2 ,2) ; CL (Covar) 5 $OMEGA 0.223144 ;kA $OMEGA 0.039221 0.039221 ;CL V $OMEGA .0001 FIXED;F $SIGMA 0.039221 ;ERR Mult $SIGMA 0.005 ;Err Add $SIGMA 1 FIXED; Random time $INPUT ID TIME AMT DV MDV EVID SS II ADDL RATD COVA $SIMULATION (-1) ONLY SUB=1 $TABLE ID RTIME AMT DV MDV2 EVID SS II ADDL RATD COVA FILE=SIMUL1 NOPRINT NOHEADER NOFORWARD $PROB Popkin Simulation 2 to generate random Concentrations $THETA (.1,1.4 ,10) ;Ka 1 $THETA (.1,3.5 ,50) ;CL 2 $THETA (1,20 ,1000) ; V 3 $THETA (1 ,1 ,1 ) ;F 4 $THETA (-2,0.2 ,2) ; CL (Covar) 5 $OMEGA 0.223144 ;kA $OMEGA 0.039221 0.039221 ;CL V $OMEGA .0001 FIXED;F $SIGMA 0.039221 ;ERR Mult $SIGMA 0.005 ;Err Add $SIGMA 1 FIXED; Random time $DATA SIMUL1 (12E12.0) NRECS=700 NOOPEN $INPUT ID TIME AMT DV MDV EVID SS II ADDL RATD COVA $SIMULATION (-1) ONLY SUB=1 $PROB Popkin Model $THETA (.1,1.4 ,10) ;Ka 1 $THETA (.1,3.5 ,50) ;CL 2 $THETA (1,20 ,1000) ; V 3 $THETA (1 ,1 ,1 ) ;F 4 $THETA (-2,0.2 ,2) ; CL (Covar) 5 $OMEGA 0.223144 ;kA $OMEGA 0.039221 0.039221 ;CL V $OMEGA .0001 FIXED;F $SIGMA 0.039221 ;ERR Mult $SIGMA 0.005 ;Err Add $SIGMA 0.01 FIXED; Random time ;Without data statement the data from the last step are used $INPUT ID TIME AMT DV MDV EVID SS II ADDL RATD COVA $ESTIM MAXEVALS=2000 SIGDIGITS=3 PRINT=0 METHOD=0 $PROB Popkin H0 $THETA (.1,1.4 ,10) ;Ka 1 $THETA (.1,3.5 ,50) ;CL 2 $THETA (1,20 ,1000) ; V 3 $THETA (1 ,1 ,1 ) ;F 4 $THETA 0.0001 FIXED; CL (Covar) 5 $OMEGA 0.223144 ;kA $OMEGA 0.039221 0.039221 ;CL V $OMEGA .0001 FIXED;F $SIGMA 0.039221 ;ERR Mult $SIGMA 0.005 ;Err Add $SIGMA 0.01 FIXED; Random time ;Without data statement the data from the last step are used $INPUT ID TIME AMT DV MDV EVID SS II ADDL RATD COVA $ESTIM MAXEVALS=2000 SIGDIGITS=3 PRINT=0 METHOD=0