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Re: PK/PD modeling - fixing population paramterers vs. fixing both pop. and individual parameters

From: Nick Holford <n.holford>
Date: Thu, 02 Feb 2012 06:12:16 +1300


These papers explore the different options for modelling PK and PD data.

Zhang L, Beal SL, Sheiner LB. Simultaneous vs. sequential analysis for
population PK/PD data I: best-case performance. J Pharmacokinet
Pharmacodyn. 2003A;30(6):387-404.
Zhang L, Beal SL, Sheiner LB. Simultaneous vs. sequential analysis for
population PK/PD data II: robustness of methods. J Pharmacokinet
Pharmacodyn. 2003B;30(6):405-16.

A variant on the IPP method is described here:
Lacroix BD, Friberg LE, Karlsson MO. Evaluating the IPPSE method for
PKPD analysis []. PAGE 19. 2010.

Its usually best to fit the PK data then fix the parameters and explore
the PKPD model without changing the PK part. Once you have a good fit
you can then try a simultaneous fit. If the PK model parameters change a
lot this may be a sign of mis-specification of the PK to PK link (Zhang


On 2/02/2012 5:15 a.m., nonmem
> Hello NONMEM Team,
> We usually try to separate PK and PD models and the reasons are
> obvious. There are different ways to separate the models. Are there
> any good references which show advantages and disadvantages of fixing
> population paramterers in the PD model ann allowing the model to
> estimate individual PK parameters vs. fixing both population and
> individual PK parameters?
> Thanks!
> Pavel

Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology& Clinical Pharmacology, Bldg 505 Room 202D
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53
email: n.holford
Received on Wed Feb 01 2012 - 12:12:16 EST

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