Drug transporters and metabolic enzymes (DMETs)

Drug transporters and metabolic enzymes represent a broad category of proteins that collectively govern the pharmacokinetics of therapeutic agents. Metabolic enzymes, such as the Cytochrome P450 (CYP) superfamily, catalyze the biotransformation of drugs into metabolites, typically to facilitate excretion (Zanger & Schwab, 2013). Drug transporters, including the ATP-binding cassette (ABC) and solute carrier (SLC) families, mediate the movement of drugs across cellular membranes, influencing absorption in the gut, distribution into tissues like the brain, and elimination via the liver and kidneys (Giacomini et al., 2010). These proteins are not typically primary therapeutic targets themselves but are critical determinants of drug safety and efficacy. Genetic polymorphisms in these proteins can lead to significant inter-individual variability in drug response, while their inhibition or induction by co-administered drugs is a major cause of clinically significant drug-drug interactions (FDA, 2020). In certain contexts, such as oncology, specific transporters like P-glycoprotein are studied as targets to overcome multi-drug resistance (Robey et al., 2018).

Other names

ADME proteinsXenobiotic-metabolizing enzymes and transportersXMETsDrug-metabolizing enzymes and transporters

Modulation of systemic and local drug concentrations through enzymatic biotransformation and membrane transport.