[NMusers] RE: Emax model

[Nick Holford]

Hi Marie,

I would like to state, in my view, that the terminology "direct" is not based 
on a clear understanding of PKPD. The terminology of direct and indirect should 
be avoided. These terms might be translated into immediate and delayed effects 
but it's better to use more precise terms to describe what you want to use your 
PKPD model to describe.

In real biology there is no such thing as an immediate effect. All drug effects 
must have some delay between changes in plasma unbound concentration and the 
development of the effect associated with that concentration. These delays may 
include distribution from plasma to the effect site, binding of the drug once 
it has reached its effect site to its receptor and transduction into a stimulus 
leading to the effect, turnover of physiological mediators that are change such 
things as the input or elimination of physiological mediators that lead to the 
observed effect.

I'd be happy to provide NONMEM code for an immediate effect with an Emax model. 
But you should think carefully before using it to describe real observed 
effects which must be delayed in relation to the   concentrations used in PK 
models.

Best wishes,
Nick

--
Nick Holford, Professor Emeritus Clinical Pharmacology, MBChB, FRACP
mobile: NZ+64(21) 46 23 53 ; FR+33(6) 62 32 46 72
email: n.holf...@auckland.ac.nz
web: http://holford.fmhs.auckland.ac.nz/

From: owner-nmus...@globomaxnm.com  On Behalf Of 
Marie Rajerison
Sent: Wednesday, 9 October 2024 2:20 pm
To: nmusers@globomaxnm.com
Subject: [NMusers] Emax model

Certaines personnes qui ont reçu cet e-mail ne reçoivent pas souvent de e-mail 
de la part de 
marie.rajeri...@corteriapharma.com. 
Pourquoi c'est important
Dear NM users,

Hope my message finds you well,
Can anyone share NM control streams for a direct Emax PK/PD model?

Thank you in advance for your help

Marie

Marie RAJERISON
PharmD PhD
Pharmacometrician
e-mail: 
marie.rajeri...@corteriapharma.com
128 rue de la Boetie
75008 Paris
France
[cid:image001.jpg@01DB1A83.AD7FBF70]

[NMusers] Re: Emax model

[Sébastien Bihorel]

Hi Marie,

You can try this GUI to generate this NONMEM code: 
https://sbihorel.shinyapps.io/pmxcode/

Best

Sebastien Bihorel

From: owner-nmus...@globomaxnm.com  on behalf of 
Marie Rajerison 
Sent: Wednesday, October 9, 2024 8:20 AM
To: nmusers@globomaxnm.com 
Subject: [External] [NMusers] Emax model

Dear NM users, Hope my message finds you well, Can anyone share NM control 
streams for a direct Emax PK/PD model? Thank you in advance for your help Marie 
Marie RAJERISON PharmD PhD Pharmacometrician e-mail: marie. rajerison@ 
corteriapharma. com


Dear NM users,



Hope my message finds you well,

Can anyone share NM control streams for a direct Emax PK/PD model?



Thank you in advance for your help



Marie



Marie RAJERISON

PharmD PhD

Pharmacometrician

e-mail: 
marie.rajeri...@corteriapharma.com

128 rue de la Boetie

75008 Paris

France

[cid:image001.jpg@01DB1A56.52A8B7A0]


 
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[NMusers] Re: Emax model

[Heine, Rob ter]

Dear Marie,

There are basically two options:


  1.  Develop a sequential PK/PD model. First you develop a PK model and you 
read out the individual predictions for concentrations (IPREDs). Then, using 
the $PRED subroutine in NONMEM in a new run you can fit an EMAX equation to 
your PD as dependent value and the IPREDs as independent value.
  2.  Alternatively, you can develop a simultaneous PK/PD model. You then 
observe the PK and PD in the same compartment using two separate lines in your 
dataset, with a column with a flag whether an observation is a PK or PD 
observation. In the $ERROR block of your model you use two different equations 
for your residual error where you let your PD error function depend on the 
individual prediction for concentration in the central compartment. A hybrid 
method would be first to develop a PK model, fix the THETA/OMEGA/SIGMA for PK 
and add the PD model to this PK model, using the error block to describe the 
relationship.

Sincerely,
Rob

Van: owner-nmus...@globomaxnm.com  namens Marie 
Rajerison 
Datum: woensdag, 9 oktober 2024 om 14:31
Aan: nmusers@globomaxnm.com 
Onderwerp: [NMusers] Emax model
Dear NM users,

Hope my message finds you well,
Can anyone share NM control streams for a direct Emax PK/PD model?

Thank you in advance for your help

Marie

Marie RAJERISON
PharmD PhD
Pharmacometrician
e-mail: 
marie.rajeri...@corteriapharma.com
128 rue de la Boetie
75008 Paris
France
[cid:image001.jpg@01DB1A56.52A8B7A0]


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