Cytochrome P450 2C8 and 2C9 (CYP2C8/9)

Cytochrome P450 2C8 (CYP2C8) and 2C9 (CYP2C9) are two critical enzymes within the human CYP2C subfamily, primarily localized in the liver and small intestine [2, 6]. They are responsible for the Phase I oxidative metabolism of approximately 20-25% of all clinically used drugs, including anticoagulants, anticonvulsants, and chemotherapeutics [10, 14]. CYP2C9 is notably the primary enzyme for metabolizing drugs with narrow therapeutic windows, such as warfarin and phenytoin, while CYP2C8 is essential for the clearance of paclitaxel and thiazolidinediones [13, 15]. Beyond xenobiotic metabolism, both enzymes catalyze the conversion of arachidonic acid into epoxyeicosatrienoic acids (EETs), which serve as vital autocrine and paracrine mediators in the cardiovascular and renal systems [1, 9]. Genetic polymorphisms in the CYP2C8 and CYP2C9 genes, which are in strong linkage disequilibrium on chromosome 10, lead to significant inter-individual variability in drug clearance and are major determinants of drug-induced toxicity and therapeutic failure [3, 17]. Consequently, these enzymes are focal points for pharmacogenetic testing and the assessment of potential drug-drug interactions during drug development [8, 16].

Other names

CYP2C8CYP2C9Cytochrome P450 2C8Cytochrome P450 2C9P450 2C8P450 2C9CPC8CPC9CYPIIC8CYPIIC9

Oxidative metabolism including hydroxylation, N-dealkylation, O-dealkylation, and epoxygenation of xenobiotics and endogenous compounds [1, 16].