Target intelligence / Profile preview

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

Target
CYP2C9, CYP2C19
Molecular classification
Enzyme, Cytochrome P450 family, Monooxygenase
01

Overview

Cytochrome P450 2C9 and Cytochrome P450 2C19 are highly clinically significant liver enzymes belonging to the CYP2C subfamily. They catalyze the oxidation of a broad range of drugs and endogenous molecules, accounting for the metabolism of 20–45% of commonly prescribed drugs. Both enzymes display notable genetic polymorphism, resulting in substantial inter-individual variability in metabolic activity and drug response. Testing for CYP2C9 and CYP2C19 genotype is central to pharmacogenomic-guided therapy, especially for drugs with narrow therapeutic index or significant risk of adverse effects. Clinical guidelines recommend genotyping as a biomarker for optimizing personalized drug selection and dosing. Their importance is underscored in cardiovascular medicine (clopidogrel, warfarin), psychiatry (selective serotonin reuptake inhibitors, tricyclic antidepressants), gastroenterology (proton pump inhibitors), and beyond

Other names
Cytochrome P450 2C9P450C2C9CYP2C subfamily member 9Cytochrome P450 2C19P450C2C19CYP2C subfamily member 19
02

Mechanism of action

Inhibition of CYP2C9/CYP2C19 leads to decreased metabolism and increased plasma levels (and toxicity) of substrate drugs; Induction of CYP2C9/CYP2C19 leads to increased metabolism and reduced efficacy; Pharmacogenetic variation alters metabolizer status: poor, intermediate, normal, rapid, ultra-rapid

03

Biological functions

Drug metabolism (phase I)Oxidation of xenobioticsMetabolism of endogenous compounds (fatty acids, steroids)Synthesis of signaling epoxides from polyunsaturated fatty acids
04

Disease associations

Cardiovascular disease (due to effects on clopidogrel and warfarin metabolism)Pharmacogenetic response/adverse drug reactionsCancer (via drug metabolism impact)Other (individual variability in drug response for psychiatric, gastrointestinal, and other disease therapies)
05

Safety considerations

Increased risk of adverse drug reactions for poor metabolizersRisk of bleeding (warfarin, clopidogrel)Subtherapeutic response (proton pump inhibitors, antidepressants)Drug–drug interactions (inducers/inhibitors can profoundly alter metabolism)Wide inter-individual variation due to genetic polymorphisms
06

Interacting drugs

warfarin

15 more in the full profile.

07

Biomarkers

Genotyping for CYP2C9 and CYP2C19 alleles (e.g., *2, *3 for both; *17 for CYP2C19 ultra-rapid)Metabolizer phenotype prediction (poor, intermediate, normal, rapid, ultra-rapid)Monitoring plasma drug and metabolite levels

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