Dear Karam

This is a simple example we used modelling endogenous and exogenous IGF-1:

https://pubmed.ncbi.nlm.nih.gov/23793696/

BW

Joe

On 6 Oct 2024, at 09:34, karam alali <ph.kar...@gmail.com> wrote:


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Thanks for your reply Jeroen,

This is an interesting approach to use the circadian rhythm of cortisol and 
then the inhibition function of exogenous hydrocortisone to link the two 
substances. However, if I do not have enough data (one point at time zero, then 
a few points after the dose, not a 24h data), do you think I can apply the same 
coding for the circadian rhythm (they used 4 harmonics)? If you have a 
reference for coding the circadian rhythm, that would be useful.

Best Regards

Karam Alali
PhD Candidate
Clinical Pharmacy Discipline
Universiti Sains Malaysia

On Sun, Oct 6, 2024 at 4:18 PM karam alali 
<ph.kar...@gmail.com<mailto:ph.kar...@gmail.com>> wrote:
Thanks for your reply Jeroen,

This is an interesting approach to use the circadian rhythm of cortisol and 
then the inhibition function of exogenous hydrocortisone to link the two 
substances. However, if I do not have enough data (one point at time zero, then 
a few points after the dose, not a 24h data), do you think I can apply the same 
coding for the circadian rhythm (they used 4 harmonics)? If you have a 
reference for coding the circadian rhythm, that would be useful.

Best Regards

Karam Alali
PhD Candidate
Clinical Pharmacy Discipline
Universiti Sains Malaysia

On Sat, Oct 5, 2024 at 3:41 PM Jeroen Elassaiss-Schaap (PD-value B.V.) 
<jer...@pd-value.com<mailto:jer...@pd-value.com>> wrote:
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<http://pd-value.com/>
jer...@pd-value.com<mailto:jer...@pd-value.com>
@PD_value
+31 6 23118438
-- More value out of your data!

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


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  • ... karam alali
    • ... Jeroen Elassaiss-Schaap (PD-value B.V.)
      • ... karam alali
        • ... Michelet, Robin
        • ... STANDING, Joseph (GREAT ORMOND STREET HOSPITAL FOR CHILDREN NHS FOUNDATION TRUST)

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