NONMEM Users Network Archive

Hosted by Cognigen

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

From: Murad Melhem <melhemmr>
Date: Tue, 9 Dec 2008 12:17:10 -0500

Hi Alan,
Like Bill mentioned above, the reason why the simultaneous approach rasises
questions is that the PK fitted with the simultaneous method can be quite
sensitive to PD model misspecification.
The publicatiosn below discussed the robusteness and performance of several
secinarios within the two methods (simultaneous vs. sequential):

1: Zhang L, Beal SL, Sheinerz LB. Simultaneous vs. sequential analysis
for population PK/PD data II: robustness of methods. J Pharmacokinet
Pharmacodyn. 2003 Dec;30(6):405-16.

2: Zhang L, Beal SL, Sheiner LB. Simultaneous vs. sequential analysis
for population PK/PD data I: best-case performance. J Pharmacokinet
Pharmacodyn. 2003 Dec;30(6):387-404.

*Murad Melhem, PhD*

*assistant Director Pk/PD*

*Cognigen Corp.*

*Buffalo, NY*


 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

Received on Tue Dec 09 2008 - 12:17:10 EST

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to:

Once subscribed, you may contribute to the discussion by emailing: