ADME/Tox analyses Drug Drug interactions

Drug Stability CYP assays

Model systems Cell Line Authentication

Isotopically labeled products

Transporters - Substrates - Inhibitors

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CYP Inhibition

Fluorescent dyes: The probe substrates used in these assays are derivatives of coumarin or resorufin, which after dealkylation by CYPs will generate fluorescent products. Because these substrates are generally not highly specific to the individual CYP isozyme confirmation studies are required to identify specific inhibition effects.

The more detailed and confirmative investigation of CYP inhibition should use traditional probe substrates, which are more specific to individual CYP isoforms. For instance, midazolam 1-hydroxylation and testosterone 6β-hydroxylation are pathways catalysed predominantly by CYP2D6. Because these substrates are more specific to individual CYP isoforms, the inhibition assays can be performed with not only the individual recombinant CYP isoform but also the liver microsomes or other tissue preparations, such as hepatocytes, which contain all CYP enzymes.

CYP Induction

Some chemicals can induce the activity of CYP enzymes. The chemical inducers will increase the metabolism of concomitant drugs that are the substrates of the induced CYP enzymes, resulting in concomitant drugs losing efficacy. CYP enzymes such as CYP1A2, CYP2B6, and CYP3A4 are susceptible to induction. The induction assays are typically performed using plateable human or rat hepatocytes