NONMEM Users Network Archive

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

From: Daren Austin <daren.j.austin_at_gsk.com>
Date: Wed, 6 Jun 2018 15:20:46 +0000

I take the post-hoc PK parameters table, read them into SAS and execute the ODE model with small time steps using proc model.

Sort the results by Cmax descending and select first observation for Cmax and Tmax.

Precision is based solely on the number of time points in the data step. The table of parameters can be expanded to include other summary measures, and is saved as a CSV file for SAS dataset for further reporting.

Kind regards,

Daren

Daren Austin
GSK Senior Fellow
Senior Director, Clinical Pharmacology
Clinical Pharmacology Modelling & Simulation
Quantitative Sciences

GSK
Stockley Park West, 1-3 Ironbridge Road, Uxbridge, Middlesex, UB11 1BT, UK
Email daren.j.austin_at_gsk.com
Mobile +44 7712 670097
Tel +44 20 89903689

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-----Original Message-----
From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of Leonid Gibiansky
Sent: 04 May 2018 00:59
To: nmusers_at_globomaxnm.com
Subject: [NMusers] Cmax/Tmax in the DES block

EXTERNAL

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 Wed Jun 06 2018 - 11:20:46 EDT

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