Drug-metabolizing enzymes and drug transporters (DMETs) (DMETs)

Drug-metabolizing enzymes and drug transporters (DMETs) are a vast group of proteins that collectively determine the pharmacokinetic profile of most therapeutic agents by managing their absorption, distribution, metabolism, and excretion (ADME) (FDA, 2023). These proteins are strategically located in organs like the liver, intestines, and kidneys to facilitate the detoxification and elimination of xenobiotics (NIH, 2022). The system includes Phase I enzymes like Cytochrome P450s, Phase II enzymes like UDP-glucuronosyltransferases, and various uptake and efflux transporters such as P-glycoprotein and OATPs (StatPearls, 2023). While they are rarely the primary intended target for treating a disease, they are critical safety targets because their modulation can lead to significant drug-drug interactions and toxicity (PubMed, 2021). Genetic variations in DMET genes are a primary cause of inter-individual differences in drug efficacy and safety, making them a cornerstone of pharmacogenomics and precision medicine (PharmGKB, 2024). Understanding the interplay between these enzymes and transporters is essential for predicting drug clearance and avoiding adverse clinical outcomes (Nature Reviews Drug Discovery, 2020).

Other names

ADME proteinsXenobiotic-metabolizing enzymesPhase I and II enzymesDrug transportersXenobiotic transporters

Drugs interact with these proteins as substrates, inhibitors, or inducers, thereby modulating the metabolic conversion and cellular transport of xenobiotics, which directly impacts systemic drug exposure and clearance (FDA, 2023).