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Impact of CYP & P-gp on bioavailability #364
Hello OSP !
I am currently working on a project with compounds that are both P-gp substrate molecules and are metabolized by CYP3A4. Some of these compounds show very low bioavailability in vivo. I am interested in using the software to determine the impact of P-gp and CYP3A4 (isolated AND combined) on bioavailability and particularly on first pass gut effect.
Has anyone tried to do this before? If so, could you share your conclusions and the information of how to explore it in PK-sim?
Many thanks in advance
I am not aware of any work that explicitly looks into estimating the impact of first-pass CYP3A4 metabolism and P-gp transport.
The closest to what you are looking for is a very recent publication on CYP3A4 and P-gp DDI in PK-Sim: Open-Systems-Pharmacology/OSP-based-publications-and-content#191
Within PK-Sim, there is no direct way to separately assess impact of the different routes (e.g. intestinal vs. hepatic) either with a sensitivity analysis or a population simulation, but you can do so after exporting the model to MoBi.
You could, of course, also do this via the Matlab or R interface with your own scripted sensitivity analysis.
Hope this helps as a start,