Re: Change in Baseline Response in a PK/PD model
Hi Francois,
I don't fully understand the physiological basis of your model, but I think
you may try to incorporate the effect of surgery on your basline in the
model as follow:
A = [ baseline current + f(t) ] * [1 + (Ce(t)/EC50)^gama]
where f(t) is a function of time, representing the effect of surgery.
Best,
Xiaofeng
Quoted reply history
On Wed, Jul 18, 2012 at 10:52 AM, Francois Gaudreault <
[email protected]> wrote:
> Dear Nmusers,
>
> I am currently working on a PK/PD model for the anesthetic effect of nerve
> blockade and I am now facing issues regarding the PD aspect of my data. I
> am using a surrogate PD endpoint (current perception threshold; CPT) to
> quantitatively assess the attenuation of the signal propagation after the
> injection of the drug. Asssuming complete anesthesia is possible, the
> attenuation (A) is modeled by an inibitory sigmoid Emax model given by :
>
> A = baseline current * [1 + (Ce(t)/EC50)^gama]
>
> where EC50 is the effect site concentration causing 50% attenuation (or
> 100% increase in stimulus intensity for response)
> Ref: Sarton et al. Anesthesiology 2000:93:1245-54.
>
> In this model, the baseline response is very important for the
> calculation of EC50. We observed that PD baseline is significantly
> different after surgery compared to time 0 (before the administration of
> the local anesthetic). I have tried several approaches to handling PD
> baseline and B1 (typical value and its eta are estimated together with
> other parameter in the model) (ref: Journ of PKPD 2008 35:269-283) is by
> far, the best one. However, it assumes that the baseline is constant for a
> given individual, which is clearly not the case in this setting.
>
> Is there any way to take into account changes in PD baseline that occur
> after surgery ? Any thoughts are welcome... By the way, IOV (interoccasion
> variability) did not improve the model fit.
>
>
>
> --
> François Gaudreault, Ph.D. Candidate
> Pharmacométrie / *Pharmacometrics**
> *Chargé de cours / *Lecturer*
> Faculté de pharmacie / *Faculty of Pharmacy
> *Université de Montréal
>
>
--
Xiaofeng Wang
Ph.D candidate
The University of Iowa
115 S. Grand Ave, Iowa City, IA 52242
Phone: 319-855-0662
Email: [email protected]