Drug-metabolizing and transport proteins (DMTPs) (DMTPs)

Drug-metabolizing and transport proteins (DMTPs) represent a comprehensive functional class of enzymes and membrane transporters that dictate the absorption, distribution, metabolism, and excretion (ADME) of drugs and endogenous substances [1]. This group includes Phase I enzymes like the Cytochrome P450 (CYP) family, Phase II enzymes such as UDP-glucuronosyltransferases (UGTs), and various transporters including P-glycoprotein (ABCB1) and Organic Anion Transporting Polypeptides (OATPs) [2, 3]. These proteins are primarily localized in the liver, intestine, and kidney, where they serve as a biochemical barrier against xenobiotics [4]. While they are rarely the primary therapeutic targets for treating disease, they are critical "antitargets" because their activity determines the systemic exposure and safety profile of nearly all pharmaceutical agents [1]. Genetic variations in DMTP genes, such as CYP2D6 or SLCO1B1, are major drivers of inter-individual variability in drug efficacy and toxicity [2]. Furthermore, the induction or inhibition of these proteins by one drug can profoundly alter the pharmacokinetics of co-administered medications, leading to clinically significant drug-drug interactions [1, 5].

Other names

Drug-metabolizing enzymes and transportersDMETsADME proteinsXenobiotic-metabolizing enzymes and transporters

Drugs interact with these proteins as substrates, inhibitors, or inducers, which alters the pharmacokinetic profile (absorption, distribution, metabolism, and excretion) of the drug or its metabolites [1, 3].