Cytochrome P450

    Cytochrome P450 (CYPs) are a diverse family of enzymes involved broadly in cellular metabolism and detoxification. CYPs are the most well-recognized drug-metabolizing enzymes in the body. Many internal and external factors can influence their level of activity, which can contribute to the risk of drug interactions.


    Cytochrome P450 (CYPs) are a superfamily of enzymes involved in cellular metabolism and detoxification. There are at least 57 known CYP enzymes with diverse functions, ranging from the synthesis and breakdown of cholesterol and various hormones to the detoxification of foreign compounds like medications, supplements, and environmental pollutants.[1] This page will focus on the CYPs involved in drug metabolism, namely: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP3A4, and CYP3A5.[2]

    CYPs are the most common drug-metabolizing enzymes and are linked to the metabolism of nearly 80% of medications.[2] In general, when a medication is metabolized by a CYP enzyme its therapeutic effects are reduced, but in some cases, the medication may be converted into a form that is more biologically active. For example, prodrugs are medications that are not active until they are metabolized by a CYP enzyme. In this way, the actions of CYPs are closely tied to the effectiveness and safety of many medications.[2] CYPs can be found in various places throughout the body, but those located in the liver and intestine are the most important for drug metabolism.[3]

    The level of activity of CYP enzymes can be influenced by a multitude of factors, including genetics, age, disease states, lifestyle factors (e.g., smoking, diet), and medications or supplements themselves. These factors collectively shape an individual's response to medication and serve as the foundation for certain types of pharmacokinetic drug interactions.[2]

    We call the molecules that CYP enzymes interact with substrates, inhibitors, or inducers.

    • Substrates are compounds that are metabolized by a given enzyme. Substrates do not necessarily increase or decrease enzyme activity.
    • Inhibitors of a given enzyme are compounds that decrease that enzyme’s activity; this can reduce drug metabolism, potentially increasing the risk of medication side effects or toxicity.. This is referred to as CYP inhibition and can lead to pharmacokinetic drug interactions.
    • Inducers of a given enzyme are compounds that increase that enzyme’s activity, again potentially reducing the effectiveness of a medication. This is referred to as CYP induction, and it can also lead to pharmacokinetic drug interactions.

    To sum up:

    Interaction with the enzymeAffects the enzyme’s activity?
    SubstrateMetabolized by the enzymeNot necessarily
    InhibitorReduce the enzyme’s activityYes (decrease)
    InducerIncrease the enzyme’s activityYes (increase)

    When someone is taking multiple medications and/or supplements, especially in the context of disease or genetic variations, these types of interactions can get really complicated really fast! That’s why it’s always best to talk with a medical professional to make sure the interventions are safe.


    1. ^Manikandan P, Nagini SCytochrome P450 Structure, Function and Clinical Significance: A Review.Curr Drug Targets.(2018)
    2. ^Zhao M, Ma J, Li M, Zhang Y, Jiang B, Zhao X, Huai C, Shen L, Zhang N, He L, Qin SCytochrome P450 Enzymes and Drug Metabolism in Humans.Int J Mol Sci.(2021-Nov-26)
    3. ^Song Y, Li C, Liu G, Liu R, Chen Y, Li W, Cao Z, Zhao B, Lu C, Liu YDrug-Metabolizing Cytochrome P450 Enzymes Have Multifarious Influences on Treatment Outcomes.Clin Pharmacokinet.(2021-May)