Re: [NMusers] Is “DOSE=0” accepted by NONMEM?

From: Alison Boeckmann <alisonboeckmann_at_fastmail.fm>
Date: Wed, 09 Sep 2015 10:11:34 -0700

Hi Zheng,

Leonid Gibiansky answered your email suggeting a non-compartmental
$PRED.
Paolo Denti gave some other ideas, including initialization of
compartment 1 with the observed value using A_0(1).

I have a different suggestion. If the drug is oral, then there is
still drug in the depot at TIME=0. Please look at the help item
for EXOGENOUS SUPPLEMENTATION EXAMPLE. The paragraph starting "For
the drug with unknown dosing history" is the one of interest. A
Steady-state infusion into the depot,ending at time 0, with a rate
modelled by a theta is used. NONMEM will adjust the theta to best
fit not only the "baseline" observation at time 0, but also the
later observations.

I've taken your fragment of data and called it dose0ss.dat
I made up a little ADVAN2 control stream called dose0ss.ctl.
NONMEM does a reasonable job of finding a minimum with this fragment.

Here is dose0ss.dat

_at_PTID DV AMT time EVID SS II RATE
2 . 0 0 1 1 0 -1
2 6.8 0 0 0 . . .
2 1.1 0 3 0 . . .
2 0 0 6 0 . . .
3 . 0 0 1 1 0 -1
3 1.08 0 0 0 . . .
3 0.16 0 3 0 . . .
3 0.03 0 6 0 . . .
3 0 0 9 0 . . .

Here is dose0ss.ctl

$PROBLEM Example of pre-existing drug.
 $INPUT ID DV AMT TIME EVID SS II RATE
 $DATA dose0ss.dat IGNORE=_at_
 $SUBROUTINES ADVAN2 TRANS2
 $PK
   KA=THETA(1)*EXP(ETA(1))
   V=THETA(2)*EXP(ETA(2))
   S2=V
   CL=THETA(3)*EXP(ETA(3))
   R1=THETA(4)*EXP(ETA(4))
 $ERROR
  A1=A(1)
  A2=A(2)
  C2=A2/V
  IPRED=F
  Y=F+ERR(1)

$THETA (0,2) (0,1) (0,1) (0,1)
$OMEGA 1 1 1 1
$SIGMA 1
$ESTIM METHOD=1
$TABLE ID TIME A1 C2 IPRED NOPRINT FILE=dose0ss.tbl
LFORMAT="(20(4X,A8))"

The first 6 columns of the table are as follows.
In the table, IPRED and C2 are computed with individual etas.
Note that they are identical and closely match the DV values at TIME=0.

TABLE NO. 1
    ID TIME A1 C2 IPRED DV
  2.0000E+00 0.0000E+00 4.0371E+00 6.8010E+00 6.8010E+00 0.0000E+00
  2.0000E+00 0.0000E+00 4.0371E+00 6.8010E+00 6.8010E+00 6.8000E+00
  2.0000E+00 3.0000E+00 1.5287E-01 1.0877E+00 1.0877E+00 1.1000E+00
  2.0000E+00 6.0000E+00 5.7889E-03 7.1662E-02 7.1662E-02 0.0000E+00
  3.0000E+00 0.0000E+00 6.4092E-01 1.0795E+00 1.0795E+00 0.0000E+00
  3.0000E+00 0.0000E+00 6.4092E-01 1.0795E+00 1.0795E+00 1.0800E+00
  3.0000E+00 3.0000E+00 2.4242E-02 1.7236E-01 1.7236E-01 1.6000E-01
  3.0000E+00 6.0000E+00 9.1695E-04 1.1333E-02 1.1333E-02 3.0000E-02
  3.0000E+00 9.0000E+00 3.4683E-05 6.0484E-04 6.0484E-04 0.0000E+00



On Sun, Sep 6, 2015, at 11:30 PM, Zheng Liu wrote:
> Dear NONMEM users,

>

> I have a group of patients, whose plasma drug levels are measured and
> known at time=0 (no further drug is given to the patients
> afterwards.). I try to know, after how long time the drug will be
> completely cleared out from these patients. Naturally I used NONMEM to
> fit the patients' V and CL, in order to get plasma concentration
> change profile.

>

> However seems NONMEM only accepts DOSE is a positive number. If
> DOSE=0, NONMEM can't perform the fitting. Can anyone kindly give me
> some suggestions to solve this problem? Thanks a lot in advance!

>

> PTIDDVAMTtimeEVID2.126.821.13263.131.0830.16330.03639
>

>
Zheng
--
  Alison Boeckmann
  alisonboeckmann_at_fastmail.fm

Received on Wed Sep 09 2015 - 13:11:34 EDT

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