NONMEM Users Network Archive

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RE: Generating Cmax at end of infusion

From: Elassaiss - Schaap, J. - <jeroen.elassaiss>
Date: Wed, 7 Apr 2010 11:52:08 +0200

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 śmol
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 =
   


________________________________

From: owner-nmusers
On Behalf Of Eleveld, DJ
Sent: Tuesday, 06 April, 2010 20:22
To: prhutson
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: owner-nmusers
Sent: Tue 4/6/2010 6:11 PM
To: NMUSERS
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




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Received on Wed Apr 07 2010 - 05:52:08 EDT

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