Cytochrome P450 enzymes and drug transporters (CYP and drug transporters)

Cytochrome P450 (CYP) enzymes and drug transporters represent the primary biochemical machinery responsible for the absorption, distribution, metabolism, and excretion (ADME) of the majority of clinical drugs. CYP enzymes, such as CYP3A4, CYP2D6, and CYP2C9, are heme-containing proteins located primarily in the endoplasmic reticulum of hepatocytes and enterocytes, where they facilitate Phase I oxidative metabolism (StatPearls, 2023). Drug transporters, including efflux pumps like P-glycoprotein (ABCB1) and uptake carriers like Organic Anion Transporting Polypeptides (OATPs), regulate the movement of molecules across biological membranes in the liver, kidneys, and blood-brain barrier (Nature Reviews Drug Discovery, 2010). Together, these systems determine the bioavailability, half-life, and tissue distribution of therapeutic agents. Genetic polymorphisms in these proteins lead to significant inter-individual variability in drug response, ranging from severe toxicity in "poor metabolizers" to therapeutic failure in "ultrarapid metabolizers" (FDA, 2020). Because many drugs act as inhibitors or inducers of these proteins, they are the central focus of clinical pharmacology and safety assessments to prevent potentially fatal drug-drug interactions (PubMed, 2021).

Other names

Phase I metabolism enzymesXenobiotic transportersDrug-metabolizing enzymes and transportersDMETMicrosomal enzymes

Drugs interact with these proteins as substrates, competitive or non-competitive inhibitors, or transcriptional inducers, thereby altering the pharmacokinetics, systemic exposure, and clearance of co-administered medications.