CYP2C9

Cytochrome P450 2C9 (abbreviated CYP2C9) is an is_associated_with::enzyme that in humans is encoded by the CYP2C9 is_associated_with::gene.

Function
CYP2C9 is an important is_associated_with::cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the is_associated_with::cytochrome P450 protein in liver microsomes (data only for antifungal). Some 100 therapeutic drugs are metabolized by CYP2C9, including drugs with a narrow therapeutic index such as is_associated_with::warfarin and is_associated_with::phenytoin and other routinely prescribed drugs such as is_associated_with::acenocoumarol, is_associated_with::tolbutamide, is_associated_with::losartan, is_associated_with::glipizide, and some nonsteroidal anti-inflammatory drugs. By contrast, the known extrahepatic CYP2C9 often metabolizes important endogenous compound such as is_associated_with::arachidonic acid, is_associated_with::5-hydroxytryptamine, and is_associated_with::linoleic acid.

Pharmacogenomics
is_associated_with::Genetic polymorphism exists for CYP2C9 expression because the CYP2C9 gene is highly polymorphic. More than 50 is_associated_with::single nucleotide polymorphisms (SNPs) have been described in the regulatory and coding regions of the CYP2C9 gene, some of them are associated with reduced enzyme activity compared with wild type in vitro.

Multiple in vivo studies also show that several mutant CYP2C9 genotypes are associated with significant reduction of in metabolism and daily dose requirements of selected CYP2C9 substrate. In fact, is_associated_with::adverse drug reactions (ADRs) often result from unanticipated changes in CYP2C9 enzyme activity secondary to genetic polymorphisms. Especially for CYP2C9 substrates such as warfarin and phenytoin, diminished metabolic capacity because of genetic polymorphisms or drug-drug interactions can lead to toxicity at normal therapeutic doses.

Allele frequencies(%) of CYP2C9 polymorphism

CYP2C9 Ligands
Most inhibitors of CYP2C9 are competitive inhibitors. Noncompetitive inhibitors of CYP2C9 include is_associated_with::nifedipine,  is_associated_with::phenethyl isothiocyanate, is_associated_with::medroxyprogesterone acetate and is_associated_with::6-hydroxyflavone. It was indicated that the noncompetitive binding site of 6-hydroxyflavone is the reported allosteric binding site of the CYP2C9 enzyme.

Following is a table of selected substrates, inducers and inhibitors of CYP2C9. Where classes of agents are listed, there may be exceptions within the class.

Inhibitors of CYP2C9 can be classified by their potency, such as:
 * Strong being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.
 * Moderate being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
 * Weak being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.