Thank you Martin Bergstrand for your insights into the problem. I have gone through the thread and other publications as well to understand more about the metabolite kinetics. I have seen some literature assuming that parent is completely metabolised to metabolite 1 and modelled parent and metabolite -1 PK model. I am just curious to know the utility of the model in such scenarios, as metabolite 2 is completely ignored in the process. I also curious to know more about previously published model where an equation was given to find out the absolute formation of metabolite for individual after oral administration of parent drug (Wu KH, Guo T, Deng CH, Guan Z, Li L, Zhou TY, Lu W. Population pharmacokinetics of modafinil acid and estimation of the metabolic conversion of modafinil into modafinil acid in 5 major ethnic groups of China. Acta Pharmacologica Sinica. 2012 Nov;33(11):1401-8.) Here is the equation f_M= vm∗AuC_o-∞ (M) / (VC∗A UC_0-∞ (P) ). I am interested to know your thoughts on the utility of this equation to other models. Thanks for your help
*Saikumar Matcha* On Wed, Aug 30, 2023 at 6:13 AM Martin Bergstrand < martin.bergstr...@pharmetheus.com> wrote: > Dear Saikumar, > > With only data following administration of the parent drug (independent > of route of administration) it is not feasible to assess the fraction of > different metabolites formed. In order to do so you need more information. > The best form of information comes from intravenous administration of the > respective metabolites of interest as well as the parent drug. In the > absence of direct access to such data the only other option comes from > utilizing prior literature data and/or mechanistic predictions based on > translational techniques (QSAR, IVIVC, physiological scaling from animals > etc.). > > You can still model the parent-metabolite(s) data in a way that describes > the plasma concentrations of each respective moiety over time i.e. without > knowing the absolute fraction that forms each metabolite. This has been > discussed in this forum previously, see for example this thread: > https://www.mail-archive.com/nmusers@globomaxnm.com/msg03964.html > > Kind regards, > > > Martin Bergstrand, Ph.D. > > Principal Consultant > > Pharmetheus AB > > www.pharmetheus.com > > > > On Wed, Aug 30, 2023 at 2:32 AM Saikumar Matcha < > drmatchasaiku...@gmail.com> wrote: > >> >> Hello All, >> >> I am working with PK profiles of parent and active metabolite. Parent >> drug was administered orally and has two metabolites (active and in >> active). I am looking for the most efficient way to understand the fraction >> of active metabolite formed when a parent drug is administered orally. Any >> help would be greatly appreciated. >> >> Thanks & Regards >> >> *Saikumar Matcha* >> *p: +1 9199045716* >> >> > *This communication is confidential and is only intended for the use of > the individual or entity to which it is directed. It may contain > information that is privileged and exempt from disclosure under applicable > law. If you are not the intended recipient please notify us immediately. > Please do not copy it or disclose its contents to any other person.* > *Any personal data will be processed in accordance with Pharmetheus' > privacy notice, available here <https://pharmetheus.com/privacy-policy/>.* >
