Cytochrome P450 occupy a central role in drug discovery, drug interactions with these enzymes can be described in three ways, metabolism, inhibition and induction. Since CYP450 metabolism is the major route for elimination of many drugs anything that interferes with that process can have profound effects. CYP450 inhibition can prolong the half-life of the given drug but can also change the exposure to any other co-administered drugs, and since particularly in the elderly [DOI], patients may be taking multiple medicines this can be a significant concern. CYP450 enzyme induction has the opposite effect, increasing levels of enzymes (and MDR1)often via activation of the Pregnane X receptor (PXR) and thus potentially lowering the exposure of the drug.
Whilst there are many CYP450 enzymes four enzymes have been selected for the OpenADMET challenge CYP3A4, CYP2C9, CYP2D6, and CYP1A2 and as the plot above shows these are the most important enzymes for drug metabolism. More details of the OpenADMET’s CYP inhibition blind challenge are on the website. https://openadmet.ghost.io/announcing-openadmets-cyp-inhibition-blind-challenge/
