PharmPK Discussion - Extrapolated AUMC

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On 18 Jul 2002 at 16:17:21, =?iso-8859-1?Q?J=E9r=F4me?= DEL CASTILLO (j.delcastillo.-a-.envt.fr) sent the message


Cheers,

I just found a bizarre thing on how WinNonlin 3.1
non-compartmental (NCA) module calculates the last trapezoid in
AUMC (predicted).

Let's say that the last measurable point of Drug X
concentration-time profile is untrustworthy, so we exclude it
from the Lambda-Z regression (not unusual: see NCA chapter in
Gabrielsson & Weiner textbook, 2nd ed.). To extrapolate AUMC to
infinity, I was expecting the NCA module to use Tlast and
Clast(predicted). Actually, it calculates this last trapezoid
with Tlast and the predicted concentration for Lambda_Z_upper
time !

Has anybody noticed this before ? What is your opinion ? What is
the correct way to extrapolate ?

Is Walt Disney alive ?

Best regards,

Jerome del Castillo

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On 19 Jul 2002 at 15:09:35, Joseph Kim (JKim.at.Pharsight.com) sent the message


Dear Jerome,
You wrote,

"I just found a bizarre thing on how WinNonlin 3.1
non-compartmental (NCA) module calculates the last trapezoid in
AUMC (predicted).

Let's say that the last measurable point of Drug X
concentration-time profile is untrustworthy, so we exclude it
from the Lambda-Z regression (not unusual: see NCA chapter in
Gabrielsson & Weiner textbook, 2nd ed.). To extrapolate AUMC to
infinity, I was expecting the NCA module to use Tlast and
Clast(predicted). Actually, it calculates this last trapezoid
with Tlast and the predicted concentration for Lambda_Z_upper
time !"

It is a bug.

WinNonlin uses predicted concentration for Lambda_Z_upper time instead
of using predicted concentration for Clast.
This bug was found and fixed for our next version (version 4.0) of
WinNonlin.

If you have any questions, please let me know.

Thank you.

Joseph Kim, Ph.D., RPh.
Pharsight, Inc.
Scientific Support
5520 Dillard Drive Suite 210
Cary
NC
27511
USA
e-mail: jkim.aaa.pharsight.com=20

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