The procedure described in the original post is working without extra
points. It is working fine, just have a small bias, and the bias seems
to be zero with ADVAN6. For all the practical purposes it can be used
without extra points. I was just surprised that it is not exact in some
cases, so extra check is warranted each time when it is used (may be we
can switch to ADVAN6 rather than ADVAN13 when computing Cmax/Cmin in the
DES block).
Latest NONMEM versions have "finedata" Utility Program that can be used
to add extra points to the dataset (nm741.pdf, page 237).
Leonid
On 5/4/2018 11:01 AM, Bob Leary wrote:
One of the problems with all of this is that the user must manually enter
artificial time points (or at least in 2007 had to do this - I don't know if
this has been fixed in
The latest NM versions) in the data set in order to evaluate the fitted model
over more grid points than are in the original data.
To get a fine grid and good resolution on Cmax and Tmax
You have to enter a lot of extra time points., which is a pain in the neck. The
various ODE routines are also remarkably sensitive to how the grid is set up.
Much better would be to have a grid generator within NMTRAN that lets you just
specify beginning and end points and number of points in the grid.
I would point out that Phoenix NLME PML has always had this capability.
Bob Leary
-----Original Message-----
From: owner-nmus...@globomaxnm.com <owner-nmus...@globomaxnm.com> On Behalf Of
Leonid Gibiansky
Sent: Thursday, May 3, 2018 7:59 PM
To: nmusers@globomaxnm.com
Subject: [NMusers] Cmax/Tmax in the DES block
Interesting experience concerning computation of Cmax and Tmax (and probably
other stats) in the DES block. We used to use this way:
http://cognigencorp.com/nonmem/current/2007-December/4125.html
Specifically, reserved the place in the memory:
$ABB COMRES=2
Set these values to zero for each new subject:
$PK
IF(NEWIND.LE.1) THEN
COM(1)=0
COM(2)=0
ENDIF
and computed Cmax/TMAX as
$DES
IF(CONC.GT.COM(1)) THEN
COM(1)=CONC
COM(2)=T
ENDIF
$ERROR
CMAX=COM(1)
TMAX=COM(2)
Recently I applied the same procedure to compute Cmax following 1 hr IV infusion.
Unexpectedly, Tmax was estimated at times > 1 hr, and Cmax was higher than 1-hr
concentration (true Cmax is at 1 hr).
After some experiments, the explanation was that Nonmem computes concentration-time
course (with infusion ON) for longer than 1 hr, and resulting Cmax/Tmax are at the end of
the "computation window" rather than at 1 hr.
Turns out that the results also depend on ADVAN routine. The largest deviation
(still small, 1-3 percents) was for ADVAN8, ADVAN9, and ADVAN13. ADVAN15 was
better but still off. ADVAN14 was almost perfect but still slightly (0.01%)
off. ADVAN6 provided correct answer (up to the precision of the output). So,
the discrepancy is small but if 1-2% difference is important, one has to be
careful when using DES block computations.
Thanks
Leonid
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