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
PK/PD modeling - fixing population paramterers vs. fixing both pop. and individual parameters
Pavel,
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 [www.page-meeting.org/?abstract=1843]. 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 2003B).
Nick
Quoted reply history
On 2/02/2012 5:15 a.m., [email protected] wrote:
> 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
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email: [email protected]
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Dear Pavel,
Yes there is, one was published online just recently:
Lacroix BD, Friberg LE, Karlsson MO.
Evaluation of IPPSE, an alternative method for sequential population PKPD
analysis.
J Pharmacokinet Pharmacodyn. 2012 Jan 21.
In addition to presenting the 2 methods you're referring to, fixing
population PK parameters or conditioning on individual PK parameters, it
includes a comparison with the simultaneous PKPD fit and introduces an
approach accounting for uncertainty in the PK parameters.
Best regards,
Elodie
--
Elodie L Plan, Pharm.D, Ph.D
Metrum Research Group, LLC
2 Tunxis Road, Suite 112
Tariffville, CT 06081
*(860) 560-3770*
*(860) 735-7043*
Quoted reply history
On 1 February 2012 11:15, <[email protected]> wrote:
> 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
>