NONMEM Users Network Archive

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Re: [NMusers] Cmax/Tmax in the DES block

From: Leonid Gibiansky <lgibiansky_at_quantpharm.com>
Date: Fri, 4 May 2018 11:32:50 -0400

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-nmusers_at_globomaxnm.com <owner-nmusers_at_globomaxnm.com> On Behalf Of Leonid Gibiansky
> Sent: Thursday, May 3, 2018 7:59 PM
> To: nmusers_at_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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Received on Fri May 04 2018 - 11:32:50 EDT

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