RE: PK and PD variability
Dear Andreas,
Perhaps one strategy would be to use the data from the previous PK/PD study and
to first fit the PK data. Then fit your nice Emax model based on the PK model
. You could fit simultaneously the PK/PD from the previous study. From this
point you have several path you can take to evaluate your PD study. You can do
a Bayesian analysis using the model from the PK/PD study to get individual
estimates. You can pool the data from the 2 studies and get population and
individual estimates or just use the model from the PK/PD study and fit it with
the data of the PD study.
Best regards,
Jean
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of [email protected]
Sent: Friday, March 11, 2011 4:47 AM
To: [email protected]
Subject: [NMusers] PK and PD variability
Dear group,
I am currently analyzing some dose-response data for one of our drugs. A simple
Emax model nicely described the dose-response relationship for the principal PD
variable (a continuous measure). Unfortunately, no PK data was obtained from
the subjects in the PD study. Since the variability in the PD measure was quite
high (CV>80% placebo, CV>100% active treatment) and variability in the AUC from
previous PK studies was also high (55%, mainly due to variable
bioavailability), the question is if reducing the variability in F (better
formulation) would also relevantly improve PD variability.
I have tried the following:
- Adding an ETA to dose in the Emax model with IIV fixed to 55%CV
(IIV_ED50 reduced from 100% to 75%)
- Use the resulting estimates (including IIV_ED50, IIV_Placebo, residual
variability,[Emax was fixed]) to simulate the response for different values of
IIV_dose
- Calculate the overall variability of the response
(Note, that residual variability was also pretty high (approx 100%CV))
The results suggested that the overall PD variability would only decrease very
little by reducing variability in F. However, I am unsure if my approach is
acceptable and would like to have some input from the group.
Thanks in advance, Andreas.
[cid:[email protected]]
Andreas Lindauer
Pharmacokineticist
Pharmacokinetics and Metabolism
R&D Center. Ferrer Internacional S.A.
Juan de Sada 32, 08028 Barcelona
Tel +34 93 509 3265
Fax +34 93 411 2764
[email protected]
www.ferrergrupo.com
[cid:[email protected]]
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