Dear Karam, See also more recent work by Bindellini et al. where mechanistic interpretations of circadian rhythm and feedback for cortisol are formalized in a modeling framework in nonmem https://pubmed.ncbi.nlm.nih.gov/38977635/
All the best, Robin Freie Universität Berlin/qPharmetra Sent from Nine<http://www.9folders.com/> ________________________________ From: karam alali <[email protected]> Sent: Sunday, October 6, 2024 10:31 To: [email protected] Subject: Re: [NMusers] Separation of the PK parameters for mixed endogenous and exogenous substances. 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 <[email protected]<mailto:[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]<mailto:[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]<mailto:[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
