Re: Separation of the PK parameters for mixed endogenous and exogenous substances.
Dear Karem,
The short answer is that it is possible to set up an useful PK model in this circumstance. The focus however will be to describe the endogenous substance with sufficient detail and quality. Only once you have done that properly you can derive a meaningful PK model for the exogenous substance.
An example can be found in the work of the Jusko group on cortisol, which is both a non-steady state biomarker and a drug (but more complicated because of feedback). See eg the Mager2013 paper: https://doi.org/10.1177/0091270003258651
Hope this helps,
Jeroen
http://pd-value.com
[email protected]
@PD_value
+31 6 23118438
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Quoted reply history
On 05-10-2024 09:02, karam alali wrote:
> Dear NONMEM users,
>
> I encountered a case when an endogenous substance and an exogenous substance were not separated by any analytical method or using isotopes, which means we have a mix of both substances in the central compartment.
>
> 1. What are the possible methods to predict their pharmacokinetics?
>
> 2. Is it valid to use the clearance and volume of distribution of the total substance? 3. if I use the central compartment for the endogenous substance DADTendo (which contains the total) and create a dummy compartment for the exogenous substance DADTexo, would then be possible to account separately for each of their pharmacokinetics (CL, V) when we set the IPRED = A(endo) + A(exo)?
>
> Note: the endogenous substances are not in a steady state
>
> Regard
>
> Karam Alali
> PhD Candidate
> Clinical Pharmacy Discipline
> Universiti Sains Malaysia