Many drugs are known to be processed by the same metabolic pathways. I’m thinking here specifically of cytochrome p450 complex.
If I have 2 drugs that are known to be metabolised by the same enzyme, and I take them both together, do they both compete for that enzyme and become metabolised more slowly? Or is there more than enough CYP34A to metabolize everything?
This isn’t for homework or medical advice… I’m just trying to determine whether something I read is accurate or represents sloppy reasoning.
I need some to ingest some caffeine, which is metabolized by cytochrome p450 1a2.
However, here’s a big table of substrates and inhibitors for the various liver P450s.
Ooooh oooooh! I just took an exam on this yesterday. There are at least two types of drug/drug interaction. One is, as you mentioned, competitive binding for the active site of an enzyme. The other is up- or down-regulation of the enzyme through the receptor. The receptor acts as a chemical detector, and increases genetic expression of its associated gene.
In the case of CYP3A4, a drug or some other organic molecule will bind the PXR receptor. PXR dimerizes with RXR and they bind to a promoter region of CYP3 genes. The transcription/translation of those genes are increased. So, if you’re taking a drug that is metabolized by CYP3A4, and 3A4 is being upregulated by something else you’re taking, both drugs will be cleared faster, meaning that the therapeutic effects will be less or non-existent.
There are also PXR antagonists that will prevent PXR transfer to the nucleus, prevent PXR-RXR dimerization or prevent PXR-RXR binding to the DNA promoter region. In this case, CYP3A4 gene expression is down-regulated and the active parent form of the drug remains in your system longer. You can be in an overdosed condition after taking a normal dose.
These two scenarios with PXR can occur with drigs, or they can occur with a drug and some environmental chemical, such as dioxin. CYP3A4 is a slut: it can metabolize a wide range of aromatic organic molecules (50% of all drugs as well), so there is plenty of opportunity for CYP3A4 expression to be affected.