Cytochrome P450 family 2 subfamily C member 9 (CYP2C9) (CYP2C9)

Cytochrome P450 family 2 subfamily C member 9 (CYP2C9) is a critical hepatic enzyme responsible for the phase I metabolism of approximately 15% of clinically significant drugs, most notably the S-enantiomer of the anticoagulant warfarin [5, 12]. As a member of the cytochrome P450 superfamily, it acts as a monooxygenase, catalyzing the 7-hydroxylation of S-warfarin into inactive metabolites, which is the primary pathway for the drug's clearance from the body [1, 11, 14]. Beyond warfarin, CYP2C9 is involved in the biotransformation of a diverse range of therapeutic agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), phenytoin, and oral hypoglycemics [3, 12]. Genetic variations in the CYP2C9 gene, such as the *2 and *3 alleles, lead to markedly reduced enzymatic activity, resulting in slower drug clearance and a significantly increased risk of over-anticoagulation and life-threatening bleeding episodes [4, 10, 16]. Consequently, CYP2C9 genotype is a major clinical biomarker used alongside the pharmacodynamic target VKORC1 to calculate personalized and safe dosing regimens for patients [9, 13].

Other names

CYPIIC9CPC9Cytochrome P450 2C9Aryl hydrocarbon hydroxylaseS-warfarin hydroxylase

Drugs interact with this enzyme primarily as substrates that undergo oxidative biotransformation, inhibitors that compete for the active site or bind irreversibly to reduce metabolic clearance, or inducers that increase enzyme expression via nuclear receptor pathways [1, 2, 6].