Re: Separation of the PK parameters for mixed endogenous and exogenous substances.

On Sun, Oct 6, 2024 at 4:18 PM karam alali <[email protected]> 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.) < > [email protected]> 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 >> [email protected] >> @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 >> >