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RE: Simultaneous vs sequential for modeling parent AND metabolites in pop PK

From: xiaofeng.wang
Date: Tue, 9 Dec 2008 15:37:03 -0500

The appropriate approach is to fit parent compound and the metabolites
simultaneously, since it can help uniquely define the PK parameters,
especially the CL. As we know that CL is a lumped parameter without
metabolite information. Sequential estimation is the approach when there
is no better way to solve the problem in simultaneous fitting due to
numerical problem.

This is different situation from PK-PD fitting. In the situation if PD
has impact on PK, also, simultaneous fitting is the way to go.

xiaofeng

Xiaofeng Wang, PhD
Oncology, Novartis
(862)778-8856 (o)



"Xiao, Alan" <Alan.Xiao
Sent by: owner-nmusers
12/09/2008 01:30 PM

To
"Bachman, William" <William.Bachman
cc

Subject
RE: [NMusers] Simultaneous vs sequential for modeling parent AND
metabolites in pop PK






Dear All,

Thanks for your response and I'm sorry for the confusion.

I'm talking about the sequential/simultaneous modeling to fit parent
concentrations AND metabolites in pop PK, not about PD data at all.

That is for sequential approach, you develop a model to fit the parent
data
 first and then fix the PK parameters for parents to develop a model
to fit the metabolite. While, for simultaneous approach, you develop a
model to
fit both parent and metabolites simultaneously
(to simultaneously estimate parameters for both parent and metabolites).

Alan

-----Original Message-----
From: Bachman, William [mailto:William.Bachman
Sent: Tuesday, December 09, 2008 11:26 AM
To: Xiao, Alan
Cc: nmusers
Subject: RE: [NMusers] Simultaneous vs sequential for modeling parent
AND metabolites in pop PK


The argument against the simultaneous approach is that the PD data can
"drive" the PK model, particulary since the PD data usually has more
variability.

-----Original Message-----
From: owner-nmusers
On Behalf Of Xiao, Alan
Sent: Tuesday, December 09, 2008 11:02 AM
To: nmusers
Subject: [NMusers] Simultaneous vs sequential for modeling parent AND
metabolites in pop PK

Dear All,

I know this is an old topic but would like to see the statistics.

When you have to develop a pop PK model for both parent and active
metabolites, which approach do you prefer or have you used most:
simultaneous or sequential? Which way do you think is more scientific? I
heard comments saying that the simultaneous approach is not scientific.

Thanks,

Alan
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Received on Tue Dec 09 2008 - 15:37:03 EST

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