CYP2C19

CYP2C19 is a member of the cytochrome P450 family of enzymes that reside mainly in the liver and also in the intestine. The enzyme is encoded by the CYP2C19 gene and participates in the oxidative metabolism of a variety of clinically important drugs, including proton pump inhibitors, certain antiplatelet agents, antidepressants, anticonvulsants, antifungals, and benzodiazepines. Its activity influences drug exposure, efficacy, and risk of adverse effects.

The CYP2C19 gene is highly polymorphic, producing a range of metabolic phenotypes. The wild-type allele, often designated as *1, enables normal (extensive) metabolism. Loss-of-function variants, such as *2 and *3, reduce or abolish enzyme activity, leading to poor or intermediate metabolizer phenotypes. A gain-of-function allele, *17, can increase enzymatic activity, contributing to ultrarapid metabolism. The distribution of these alleles varies by ethnicity, contributing to interindividual and cross-population differences in drug response.

Clinically important implications include the activation of the antiplatelet prodrug clopidogrel, where poor metabolizers may have reduced platelet inhibition and higher cardiovascular risk. Proton pump inhibitors and voriconazole are also affected, with altered drug exposure in poor or ultrarapid metabolizers. Depending on the drug and patient genotype, dosing or alternative therapies may be recommended. Drug–drug interactions can further modify CYP2C19 activity; inhibitors can elevate exposure, while inducers can enhance clearance.

Genetic testing for CYP2C19 can guide personalized therapy for selected drugs. CPIC and other guidelines summarize how genotype information should influence prescribing, though testing is not routinely required for all medications. As pharmacogenomic knowledge evolves, CYP2C19 remains a key example of genotype-driven precision medicine.