Cytochrome P450 2C9 and Cytochrome P450 2C19 (CYP2C9/CYP2C19)

Cytochrome P450 2C9 (CYP2C9) and Cytochrome P450 2C19 (CYP2C19) are major phase I drug-metabolizing enzymes within the CYP2C subfamily, primarily located in the liver [1.1.4, 1.2.2]. This entry refers to two distinct enzymes that are often grouped together due to their shared genomic location on chromosome 10 and their collective role in metabolizing approximately 20-25% of clinical drugs [1.1.4, 1.4.2]. CYP2C9 is the principal enzyme for the metabolism of narrow therapeutic index drugs such as S-warfarin and phenytoin, whereas CYP2C19 is critical for the bioactivation of the antiplatelet prodrug clopidogrel [1.1.4, 1.3.2]. Both enzymes are highly polymorphic, leading to phenotypes (poor, intermediate, normal, and ultra-rapid metabolizers) that significantly impact drug efficacy and safety [1.1.3, 1.4.1]. Genetic variations in these enzymes are associated with adverse clinical outcomes, including major bleeding or therapeutic failure, making them primary targets for pharmacogenetic testing and the optimization of personalized medicine [1.1.1, 1.3.2]. In addition to drug metabolism, these enzymes participate in the oxidation of endogenous compounds such as arachidonic acid and steroids [1.3.1, 1.4.1]. Drug-drug interactions involving these enzymes are a major clinical concern, as inhibition or induction by one drug can lead to toxic levels or subtherapeutic concentrations of another [1.1.2, 1.2.2].

Other names

Cytochrome P450 family 2 subfamily C member 9Cytochrome P450 family 2 subfamily C member 19CPC9CPC19CYP2C10CYPIIC9CYPIIC19P450-2C9P450-2C19

These enzymes catalyze the phase I oxidative metabolism of a wide range of substrates through hydroxylation, dealkylation, and epoxidation reactions. They are also responsible for the bioactivation of prodrugs, most notably the conversion of clopidogrel to its active antiplatelet metabolite [1.1.4, 1.3.2].