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[NMusers] Cmax/Tmax in the DES block

From: Leonid Gibiansky <lgibiansky_at_quantpharm.com>
Date: Thu, 3 May 2018 19:59:29 -0400

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


Received on Thu May 03 2018 - 19:59:29 EDT

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