Abstract
Drug-drug interaction (DDI) is the change in a drug’s pharmacological activity when co-administered with another drug. Here, we present a clear explanation of interaction of drugs through CYP induction from a systematic review of several research articles. Drug-drug interaction via CYP induction takes place in two ways; via nuclear receptors and by stabilization of the enzyme or mRNA. The identified issues include reduced comedication therapeutic efficiency and increased reactive metabolite-induced toxicity. This paper concludes that it is necessary to develop novel treatment options that are not strong CYP inducers in order to reduce the possibility of drug-drug interactions caused by CYP induction.
Introduction
Generally, the aspect of Drug-Drug Interactions (DDIs) is significant and requires close evaluation to comprehend the reactivity of different drugs via CYP. When medicines are co-administered, their pharmacological activity is likely to change which might affect their effect in the body. Therefore, it is necessary to develop effective medicines that do not induce CPY when used together with other drugs to lower the occurrence of CPY induction that can reduce drug efficacy.
Discussion
Drug-drug interactions (DDIs) are a serious concern because they can lead to unfavorable drug reactions and unwanted therapeutic effects. There are two categories of DDIs which include pharmacokinetic and pharmacodynamic. Pharmacokinetics is the most prevalent type of DDI (Dmitriev et al., 2019). The main mechanisms producing pharmacokinetic drug-drug interactions are the inhibition and induction of CYPs (Hendriks et al., 2020). Cytochrome P450 (CYP) enzyme family is the most important enzyme system for catalyzing the phase 1 metabolism of drugs and other xenobiotics, such as herbal remedies and environmentally hazardous chemicals. (Hakkola et al., 2020). Due in part to drug-drug and drug-gene interactions, several clinically important DDIs are associated with interactions with (CYP) enzymes.
By boosting enzyme production, inducers raise CYP450 enzyme activity. Depending on the half-life of the provoking substance, there is typically a delay preceding a rise in enzyme activity. When phenobarbital, an inducer with a very long half-life, is started, a drop in the quantity of a substance that CYP2C9 metabolizes can happen up to one week later than when rifampin (Rifadin), an inducer with a short half-life, is started (Tornio, 2019). The same CYP450 enzyme that a drug activates may also be used in its metabolism. As its half-life rapidly shortens over time, carbamazepine (Tegretol), a strong enzyme inducer, must be started at a low dose and then raised at weekly intervals.
There are two primary ways that cytochrome P450 enzymes might be induced. Firstly, they can be induced via nuclear receptors (Ritter et al., 2020). Drug-induced alterations in the expression of phase I and phase II enzymes and transporters are mediated by nuclear receptors, including the aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR) (Ritter et al., 2020). A strong representative endpoint for the activation of AhR, CAR, and PXR, respectively, can be the induction of CYP1A2, CYP2B6, and CYP3A4 gene expression.
The second way is through stabilization of the enzyme or mRNA. Troleandomycin, for instance, stimulates rat CYP3A by lowering the rate of CYP3A protein breakdown while leaving protein synthesis unchanged (Feldman, 2020). An example of CYP inducers is when antiretroviral treatments are administered alongside corticosteroids for HIV, it may result in chronic toxicities (Cadet, 2021). In order to prevent the possibility of CYP induction-mediated drug interactions, there is need to develop better drugs that are not strong CYP inducers (Chen et al., 2022). Due to this, several pharmaceutical companies now routinely evaluate CYP induction during the drug research stage as part of the screening procedures.
Conclusion
Drug-drug interaction is the change in a drug’s pharmacological activity when it links with another drug in the body. The two types of drug-drug interaction include pharmacokinetic, and pharmacodynamic. Drug-drug interaction via CYP induction presents occur in two ways. The first one is through nuclear receptors while the other way is by stabilizing the enzyme or the mRNA. Therefore, designing innovative therapeutic drugs that are not strong CYP inducers is desirable to prevent the likelihood of drug-drug interaction through CYP induction.
Reference List
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