CYP2C9

CYP2C9 Full Name

cytochrome P450, family 2, subfamily C, polypeptide 9

CYP2C9 Introduction

CYP2C9 is one of the most important drug-metabolizing enzymes in humans. It belongs to the CYP2C gene cluster, along with CYP2C8, CYP2C18, and CYP2C19. This enzyme is predominantly expressed in the liver, where it represents the second most abundant CYP enzyme, accounting for about 20% of total hepatic CYP content. It is also found in various extrahepatic tissues, including the intestine, cardiovascular system (e.g., aorta, coronary arteries), kidneys, testes, adrenal glands, prostate, brain, and uterus. Functionally, CYP2C9 is responsible for the oxidative metabolism of more than 100 commonly used drugs—such as anticoagulants, antiepileptics, NSAIDs, sulfonylureas, and angiotensin II receptor blockers—as well as endogenous molecules like steroid hormones, melatonin, retinoic acid, and arachidonic acid.

Figure 1. CYP2C9 gene locus. (Source: Sangkuhl K, et al. 2021)

Genetic variation in CYP2C9 is a major determinant of interindividual variability in drug therapy. The *2 (Arg144Cys) and *3 (Ile359Leu) alleles are the most common variants, both resulting in significantly reduced enzyme activity. In warfarin dosing, patients carrying either the CYP2C9*2 or *3 allele exhibit decreased warfarin metabolism, requiring 20%–40% lower maintenance doses on average compared to wild-type patients. In cardiovascular disease, the relationship between CYP2C9 polymorphisms and conditions such as coronary heart disease remains inconsistent. Some studies suggest that poor metabolizers may have increased cardiovascular risk due to altered arachidonic acid metabolism and endothelial function, though large-scale meta-analyses have not confirmed a significant overall association.

CYP2C9 genotyping is increasingly used in clinical practice to guide personalized dosing—classifying patients as rapid, intermediate, or poor metabolizers. Moreover, its expression in extrahepatic tissues suggests roles in local drug metabolism and physiological regulation, opening new avenues for multi-organ protective strategies.

Alternate Names for CYP2C9

CYP2C9; cytochrome P450, family 2, subfamily C, polypeptide 9; CPC9; CYP2C; CYP2C10; CYPIIC9; P450IIC9; cytochrome P450 2C9; cytochrome P-450MP; cytochrome P450 PB-1; microsomal monooxygenase; xenobiotic monooxygenase; flavoprotein-linked monooxygenase; cytochrome P-450 S-mephenytoin 4-hydroxylase;

• 1. Sangkuhl K, et al. PharmVar GeneFocus: CYP2C9. Clin Pharmacol Ther. 2021 Sep;110(3):662-676.
  2. Chang WC, et al. An update on CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Expert Opin Drug Metab Toxicol. 2020 Aug;16(8):723-734.