CYPmediated

CYPmediated metabolism refers to the biochemical processes in which cytochrome P450 enzymes catalyze the oxidative metabolism of drugs, pollutants, and endogenous compounds. This enzymatic system is a major component of phase I metabolism and contributes to the clearance and bioactivation of many xenobiotics.

Cytochrome P450 enzymes are heme-containing monooxygenases located predominantly in the liver, with significant expression in the intestine, kidney, lungs, and other tissues. They catalyze substrate hydroxylation and other oxidative reactions, using NADPH and molecular oxygen to introduce polar functional groups that facilitate renal or biliary excretion. The resulting metabolites are often more water-soluble but can also be pharmacologically active or toxic.

Major isoforms with clinical relevance include CYP3A4/5, CYP2D6, CYP2C9, CYP2C19, and CYP1A2, among others. CYP3A4 is among the most important due to its broad substrate range.

Genetic variability in CYP enzymes leads to different metabolizer phenotypes (poor, intermediate, extensive, ultrarapid), influencing drug response and adverse effects. Examples include CYP2D6 poor metabolizers with reduced codeine activation and CYP2C19 poor metabolizers with diminished activation of clopidogrel.

Drug interactions commonly involve CYP-mediated metabolism. Induction (e.g., by rifampin or anticonvulsants) can accelerate clearance and reduce drug levels, while inhibition (e.g., by ketoconazole, macrolide antibiotics) can raise levels and toxicity risk. Pharmacogenetic testing and phenotyping are used to guide dosing in certain therapies.

CYP-mediated metabolism is complemented by other pathways and is subject to age, disease, diet, and environmental factors. It remains a key area in pharmacology, toxicology, and personalized medicine.