RE: Cmax/Tmax in the DES block
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
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-----Original Message-----
From: [email protected] [mailto:[email protected]] On
Behalf Of Leonid Gibiansky
Sent: 04 May 2018 00:59
To: [email protected]
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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