Re: enzyme auto inhibition PK model
Thanks Murad,
I read the article you suggested tonight. this is the first paper I read so
far modeled enzyme auto-inhibition and it is really useful. it is also nice
to see that the article differentiate the inhibitable CL and non-inhibitable
Cl. but I am wondering if these two CL could be accurately estimated without
corresponding metabolites data? also, I still could not figure out what the
inhibition component refers to physiologically?
and why def equation for the auto-inhibition comparment was written as:
dA4/dt=Kic*( A2 / V2-A4)
isn't unit of A2 and A4 the same?
Can anyone give me some hint?
Sincerely,
Yuyan
Quoted reply history
On 6/5/08, Murad Melhem <[EMAIL PROTECTED]> wrote:
>
> 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*
>
>
> 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
>>
>
>
--
Yuyan Jin