Hello Leonid,
Thank you bein helpful. You got the main point. AUC is a better
predictor than concentration, but it has to disppear very slowly but
surely.
A potential challenge is biological meaning of this approach. It will
be necessary to explain it to the biologists, who ask question like "Why
do you use 2 compartment in PK model while human body has so many
compartments?".
We will see!
Thanks,
Pavel
On Wed, Jan 15, 2014 at 01:19 AM, lgibian...@quantpharm.com wrote:
Pavel,
I think one can use equation
DADT(2)=C-K0*A(2)
where C is the drug concentration. When K0=0, A2 is cumulative AUC.
When
k0>0, A2 would represent something like AUC for the interval prior to
the current
time
The length of the interval would be proportional to 1/K0 (and equal to
infinity when k0=0). Conceptually, K0 is the rate of "AUC elimination"
from the
system. PD then can be made dependent on A2, and the model would
select optimal
value of K0. One interesting case to understand the concept is when C
is constant.
Then A2=C/K0 while AUC over some interval TAU is AUC=C*TAU. So
roughly, A2 can
be interpreted as AUC over the interval of 1/K0. Leonid
Original email:
-----------------
From: Pavel Belo non...@optonline.net
Date: Tue, 14 Jan 2014 13:45:18 -0500 (EST)
To: robert.ba...@iconplc.com, nmusers@globomaxnm.com
Subject: [NMusers] backward integration from t-a to t
Dear Robert,
Â
Efficacy is frequently considered a function of AUC. (AUC is just
an integral. It is obvious how to calculate AUC any software which can
solve ODE.) A disadvantage of this model of efficacy is that the
effect is irreversable because AUC of concentration can only
increase; it cannot decrease. In many cases, a more meaningful model
is a model where AUC is calculated form time t -a to t (kind of
"moving average"), where t is time in the system of differential
equations (variable T in NONMEM).  There are 2 obvious ways to
calculate AUC(t-a, t). The first is to do backward integration, which
looks like a hard and resource consuming way for NONMEM. The second
one is to keep in memory AUC for all time points used during theÂ
integration and calculate AUC(t-a,t) as AUC(t) - AUC(t-a), there
AUC(t-a) can be interpolated using two closest time points below and
above t-a.Â
Â
Is there a way to access AUC for the past time points (> integration
routine? It seems like an easy thing to do.  Â
Â
Kind regards,
Pavel Â
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