Drug-drug interactions (DDI) or herb-drug interactions (HDI) are a significant concern in healthcare as they could lead to serious adverse effects. MyGenome has now included in vitro testing for evaluation of potential risk for such interactions, with particular focus on cytochrome P450 enzyme inhibition.
Cytochrome P450 enzymes (CYPs) act like factory workers in the liver to break down these compounds. There are eight major human CYP enzymes (CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2C19, CYP2B6, CYP2C8, CYP2E1) responsible for metabolizing 97% of drugs in the market.
When two or more drugs are taken concurrently, drug-drug interactions (DDI) could occur resulting in alteration of the concentration (pharmacokinetic changes) and/or function (pharmacodynamic changes) of any of the drugs. Herbal products or supplements share the same metabolic processes. Many of these products contain bioactive compounds that could inhibit or induce the CYP enzymes, hence delaying or enhancing the drug metabolism process. This can affect the level of the drug in the body, potentially leading to ineffective therapeutic responses or adverse effects. The mechanism of drug-drug or herb-drug interaction (HDI) can be explained through the Drug Plasma Concentration graph.
To be most effective, the plasma concentration of a drug should remain within the therapeutic range (green). At lower concentrations, the drug may not exert sufficient therapeutic response (orange). At higher concentrations, it may cause toxicity or adverse effects (red). Concurrent use of drug and herbal product could thus lead to low drug therapeutic response or higher risk of adverse effects. Below are examples of well-documented HDI:
We offer inhibition assays for the following CYP enzymes
Test system: Human liver microsome
Analysis Method: Quantification using LC-MS/MS following FDA regulatory guidelines
Customization: Tailored assay conditions (please contact our service agents)
Data provided: Inhibitory potential of your product (IC50 value) in comparison with enzyme-specific standard inhibitor (FDA approved)
If your product contains bioactive compounds or bioactive herbal components, there is a likelihood that your product could interact with specific drug metabolism. Identifying CYP inhibition/induction potential is critical for:
Diltiazem inhibits human intestinal cytochrome P450 3A (CYP3A) activity in vivo without altering the expression of intestinal mRNA or protein: https://doi.org/10.1111/j.1365-2125.2005.02343.x
Food drug interactions with fruit juices: https://doi.org/10.3390/foods10010033
Dose‐dependent induction of CYP3A activity by St. John’s wort alone and in combination with rifampin: https://doi.org/10.1111/cts.70007
In vitro inhibition of human cytochrome P450 enzymes by licoisoflavone B from Glycyrrhiza uralensis Fisch. ex DC: https://doi.org/10.1093/toxsci/kfad079
