RE: [NMusers] backward integration from t-a to t

[Pavel Belo]

Hello Leonid,

I agree that the effect compartment model somewhat resembles the ALAG 
approach.  Sometimes they can provide very similar outcome.  We have the 
resolution and I'll update you when it is appropriate.  Unfortunately, I 
cannot reveal some information right now.  Thanks!

Kind regards,
Pavel


On Thu, Jan 16, 2014 at 07:29 PM, lgibian...@quantpharm.com wrote:

Hi Pavel,
You mentioned that the effect compartment did not help, and the model 
I suggested is identical to the effect compartment. May be try 
something like transit compartment model:

DADT(2)=C-K0*A(2)
DADT(3)=K0*A(2)-K0*A(3)
...
DADT(X)=K0*A(X-1)-K0*A(X)

AUCapprox=A(2)+...+A(X)

This will prolong the shape of AUCapprox(t). It could be a bit simpler 
and smoother than tlag implementation Leonid






Original email:
-----------------
From: Pavel Belo non...@optonline.net
Date: Thu, 16 Jan 2014 13:05:54 -0500 (EST)
To: lgibian...@quantpharm.com, nmusers@globomaxnm.com
Subject: RE: [NMusers] backward integration from t-a to t


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 the 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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