RE: Generating Cmax at end of infusion

From: Jeroen Elassaiss-Schaap Date: April 07, 2010 technical Source: mail-archive.com
Hi Douglas, Paul, The help on mtime suggests that it should work. " When the time is reached, indicator variables are set and a call to PK is made. At this call (and/or subsequent to this call) PK or DES or AES or ERROR can use the indicator variables to change some aspect of the system, e.g., a term in a differential equation, or the rate of an infusion. This feature may be used with any ADVAN routine. " The following code (tested with nm6.2.0) however does not work in the $ERROR block, where the model predictions are available. As one can see, CP is only set at the data time event, not at the MTIME. CP2 is not set at all. So it seems $ERROR is not called upon the MTIME event. An indicator in $PK works properly (tested, not shown). Can anyone confirm this behavior? If so, this looks like a bug to me. Best regards, Jeroen ____model____ $PROB structural model 1comp.rep single subject $INPUT ID TIME DV AMT EVID TRT $DATA iv_ss.csv IGN=I $SUBR ADVAN1 TRANS2 $PK TVCL=THETA(1) CL=TVCL TVV=THETA(2) V=TVV S1=V/1000 ;mtime piece MTIME(1)=.075 ; .075 h not in dataset MTIME(2)=.5 ; .5 h not in dataset IF(TIME.EQ.0)CP=0 IF(TIME.EQ.0)CP2=0 $ERROR IPRED=F Y=F+F*ERR(1) IF(TIME.EQ.0)MYFLAG=0 ; 0 h IN dataset IF(MPAST(1).EQ.1.AND.MYFLAG.EQ.0)THEN CP=F MYFLAG=1 ENDIF CP2=CP2+MNEXT(2)*F $THETA (0,10) (0,1) $OMEGA .05 $SIM (123456789) $EST PRINT=1 MAXEVAL=9990 SIG=3 NOABORT METHOD=0 ;$COV PRINT=E $TABLE ID TIME CP CP2 IPRED NOPRINT ONEHEADER FILE=1cmp.txt ____dataset___ ID,time h,conc nM,amt,evid,dose æmol 1,0,.,30,1,10 1,0.05,0,.,0,10 1,0.166666667,0,.,0,10 1,0.333333333,0,.,0,10 1,0.683,0,.,0,10 1,1,0,.,0,10 1,2,0,.,0,10 1,4,0,.,0,10 1,8,0,.,0,10 ____table file_____ TABLE NO. 1 ID TIME CP CP2 IPRE DV 1.0000E+00 0.0000E+00 0.0000E+00 0.0000E+00 3.2044E+04 0.0000E+00 1.0000E+00 5.0000E-02 0.0000E+00 0.0000E+00 1.9459E+04 1.6272E+04 1.0000E+00 1.6667E-01 6.0768E+03 0.0000E+00 6.0768E+03 7.7936E+03 1.0000E+00 3.3333E-01 6.0768E+03 0.0000E+00 1.1524E+03 1.0149E+03 1.0000E+00 6.8300E-01 6.0768E+03 0.0000E+00 3.5213E+01 2.8321E+01 1.0000E+00 1.0000E+00 6.0768E+03 0.0000E+00 1.4905E+00 1.5249E+00 1.0000E+00 2.0000E+00 6.0768E+03 0.0000E+00 6.9328E-05 7.8605E-05 1.0000E+00 4.0000E+00 6.0768E+03 0.0000E+00 1.4999E-13 1.5736E-13 1.0000E+00 8.0000E+00 6.0768E+03 0.0000E+00 7.0211E-31 6.9514E-31
Quoted reply history
________________________________ From: [email protected] [mailto:[email protected]] On Behalf Of Eleveld, DJ Sent: Tuesday, 06 April, 2010 20:22 To: [email protected]; [email protected] Subject: RE: [NMusers] Generating Cmax at end of infusion Hi, As others have suggested making an additional record at the known desired time is probably the most straightforward manner to get what you want. So this should probably be a preferred solution. If you for some reason you cant to add a record (maybe you dont know the time beforehand), I think you can achieve what you want using MTIME(). This has the added advantage of working without going the $DES route and the associated slower run-times. I'll see if I can get something like that to work tomorrow, just as an excercise. Can the experts give an opinion as to whether MTIME() should work or not? Regards, Douglas Eleveld -----Original Message----- From: [email protected] on behalf of Paul Hutson Sent: Tue 4/6/2010 6:11 PM To: [email protected] Subject: [NMusers] Generating Cmax at end of infusion G'day. I would like to generate a concentration at the end of an infusion of duration DUR. I am using ADVAN3 TRANS4 with log transformed data. Here is what I have tried, but I am getting an error that the parameter 'T' that I understood to be the machine time is undefined. Can anyone suggest a proper way to give set Cmax=exp(Y) at the end of the infusion of length DUR? Many thanks in advance. Paul $PK ... TT=TIME $ERROR ;I've also tried ;TT=TIME ;TT=T IPRE=F EDV=EXP(DV) W=1 IF(F.GT.0) W=F IRES=F-EDV IWRE=IRES/W LOGF=LOG(0.0001) IF (F.GT.0) LOGF=LOG(F) Y=LOGF+EPS(1) ;GENERATE CMAX AT END OF INFUSION (DUR) IF(DUR.EQ.TT) CMAX=EXP(Y) -- Paul R. Hutson, Pharm.D. Associate Professor UW School of Pharmacy 777 Highland Avenue Madison WI 53705-2222 Tel 608.263.2496 Fax 608.265.5421 Pager 608.265.7000, p7856 ________________________________
Apr 06, 2010 Paul Hutson Generating Cmax at end of infusion
Apr 06, 2010 Leonid Gibiansky Re: Generating Cmax at end of infusion
Apr 06, 2010 Bill Denney RE: Generating Cmax at end of infusion
Apr 06, 2010 Steve Olson RE: Generating Cmax at end of infusion
Apr 06, 2010 Nick Holford Re: Generating Cmax at end of infusion
Apr 06, 2010 Doug J. Eleveld RE: Generating Cmax at end of infusion
Apr 07, 2010 Jeroen Elassaiss-Schaap RE: Generating Cmax at end of infusion
Apr 07, 2010 Jeroen Elassaiss-Schaap RE: Generating Cmax at end of infusion
Apr 07, 2010 Leonid Gibiansky Re: Generating Cmax at end of infusion