Time after dose

Hi, Everyone: I am having trouble with getting the correct output of TAD (time after dose) and hoping to get your suggestions. Here is a brief description of my dataset: drug was given multiple dosing every 12 hours. All the dosing events were recorded in the input file. Observations were taken right before the last dose (predose), and 0.5, 1, 2, 4, 8 hrs post-dose. I have used this code to calculate the TAD IF(AMT.GT.0) THEN TDOS=TIME TAD=0.0 ENDIF IF (AMT.EQ.0) TAD=TIME-TDOS In the output, the TADs calculated for the predose observation, instead of being a negative value, are closed to 12 and larger than the one for 8 hrs observations. It is obviously wrong and it give me wrong individual plots. I tried to find useful information in NM archive but cannot find any that suitable for my situation. Any suggestions are greatly appreciated! Thank you in advance for your help! Siwei

Dear Siwei, You may consider to add a column TAD in you NONMEM dataset. If should be pretty easy to calculate it in Excel. Best regards, Jean

Siwei, Nonmem computes the time from the most recent dose (which is in the past). It has no information about future doses, thus it cannot give you negative values. If you know the inter-dose interval (12 hours?), you can subtract it from TAD value to get the negative value (relative to the reference dose that you would like to use). Leonid -------------------------------------- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web: www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel: (301) 767 5566

Hi Siwei, Here is an example on how to get the TAD out in to table, that I've use for tutorial and which is a slight modification of that found on the Globamax webpage. http://www.globomaxnm.com/nonmem_tip3.htm Best Regards Kim Kristensen ID,TIME,DV,AMT,II,ADDL,EVID,CMT,MDV 1,0,0,4000,12,2,1,1,1 1,1,0.1,0,0,0,0,2,0 1,11,0.1,0,0,0,0,2,0 1,13,0.1,0,0,0,0,2,0 1,35,0,4000,0,0,1,1,1 1,37,0.1,0,0,0,0,0,0 2,0,0,4000,12,2,1,1,1 2,3,0.1,0,0,0,0,2,0 2,8,0.1,0,0,0,0,2,0 2,15,0.1,0,0,0,0,2,0 2,35,0,4000,0,0,1,1,1 2,39,0.1,0,0,0,0,2,0 $PROBLEM Creating TAD $INPUT ID TIME DV AMT II ADDL EVID CMT MDV $DATA TAD.csv IGN=@ $SUBROUTINES ADVAN2 TRANS2 $PK ;replace this TAD code with yours for ADDL TAD's IF(NEWIND.LT.2) THEN IFL=0 TAD=0.0 ENDIF IF(EVID.EQ.1.OR.EVID.EQ.4) THEN TDOS=TIME TAD=0.0 IFL=1 ENDIF IF(IFL.EQ.1.AND.EVID.NE.1.AND.EVID.NE.4)TAD=TIME-TDOS TVCL=THETA(1) ;Population CL TVV=THETA(2) ;Population V2 TVKA=THETA(3) ;Population KA CL = TVCL*EXP(ETA(1)) ; Individual CL V = TVV*EXP(ETA(2)) ; Individual V2 KA = TVKA*EXP(ETA(3)) ; Individual KA S2=V ; Scaling ;Secondary parameters K=CL/V THAL=0.693/K AUC=AMT/CL $ERROR IPRED = F IRES = DV-IPRED DEL = 0 IF (IPRED.EQ.0) DEL=1 IWRES = (1-DEL)*IRES/(IPRED+DEL) Y = F*(1+ERR(1)) $THETA (0,3.5,) ;CL pop $THETA (0,4.,) ;V pop $THETA (0,.6,) ;KA pop $OMEGA .09 ; CL BSV $OMEGA .09 ; V BSV $OMEGA .09 ; KA BSV $SIGMA .09 ; Propportional Error ;$EST MAX=9999 METHOD=1 INTERACTION NOABORT POSTHOC PRINT=5 ;$COV PRINT=E $TABLE ID TIME DV AMT II ADDL EVID CMT MDV TAD IPRED IRES IWRES ETA1 ETA2 ETA3 NOPRINT ONEHEADER FILE=sdtab1 ;Standard table - Goodness of fit $TABLE ID CL V KA NOPRINT ONEHEADER FILE=patab1 ;Standard first line table