Re: enzyme auto inhibition PK model
Hi Yuyan,
Mechanistic models incorporating an auto-inhibition component would be more
desirable. However, you may be able to describe the PK data of your compound
empirically by adding an additional inhibition compartment. Depending on the
concentration in this empirical compartment, systemic CL from the central
compartment is inhibited. Over time, you can allow the CL to take
values between
0 and 100% of the original value estimated for the time of the first
administration.
A good reference for such an empirical approach is:
Plock N, Buerger C, Joukhadar C, Kljucar S, Kloft C. Does linezolid inhibit
its own metabolism? Population pharmacokinetics as a tool to explain the
observed nonlinearity in both healthy volunteers and septic patients. Drug
Metab Dispos. 2007 Oct;35(10):1816-23.
I hope this helps.
*Murad Melhem, PhD*
*Assistant Director PK/PD*
*Cognigen Corporation*
*Buffalo, NY*
Quoted reply history
On Thu, Jun 5, 2008 at 5:06 PM, Yuyan Jin <[EMAIL PROTECTED]> wrote:
>
> Hi Dear Nonmem user,
>
> I am trying to model the kinetics of a compound that exhibits enzyme
> auto-inhibition.I have found some previously suggested literature by nonmem
> users, but all of them were auto-induction cases. Does anyone know any
> enzyme auto-inhibition PK model paper published ?
>
> Thanks so much!
>
> Sincerely,
> Yuyan Jin
> Graduate student
> University of Pittsburgh
>