# RE: Subpopulation

From: Serge Guzy <GUZY>
Date: Wed, 13 Aug 2008 08:52:58 -0700

Did you try to fit a non linear model with both linear (non target
specific) and non linear (target specific) clearance? At high doses, the
non linear part of the clearance will allow one estimating both vm and
Km. At low doses, Vm.C/(C+KM) will be reduced to Vm/Km.C which is now an
additional linear clearance term. When using a population approach, not
all the parameters must be identifiable for each patient unlike the
traditional individual fitting procedures (like Winnonlin).

Best regards;

Serge Guzy

Principal Scientist, XOMA (US) LLC

President, CEO, POP-PHARM; Inc;

________________________________

From: owner-nmusers
On Behalf Of saik.urien.svp
Sent: Wednesday, August 13, 2008 1:59 AM
To: Huali Wu; nmusers
Subject: Re: [NMusers] Subpopulation

Huali

The best solution is to fit all of your data to the more general model.

In this case that is of course the non linear model

(the pk linear model is a simplification of the limit where cc is very
small relative to Km)

Saik

----- Original Message -----

From: Huali Wu <mailto:hualiw

To: nmusers

Sent: Tuesday, August 12, 2008 6:14 PM

Subject: [NMusers] Subpopulation

Dear NMusers:

I am trying to fit a dataset with 13 dose levels. The highest
dose is about 10 times of the lowest dose. Each patient receive one dose
and were sampled intensively up to 7 days. The results of individual PK
analysis shown linear kinetics for some of the patients and nonlinear
kinetics for the other patients. I have tried to fit all of them
together. But my advisor wants me to fit linear patients and nonlinear
patients separately to get a better look of fitting.

Additionally, all the nonlinear patients are from higher dose
levels. But not all the patients in higher dose levels shown nonlinear
kinetics. So my question is which way is more appropriate in this case?
Should I fit them all together or separately? Could these two types of
patients be considered as subpopulations?

Any comment or suggestion will be highly appreciated.

Best regards,

Huali

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Received on Wed Aug 13 2008 - 11:52:58 EDT

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