Cytochromes P450 enzymes are essential for the metabolism of many medications, the major phase I enzymes including: CYP2C9, CYP2C19, and CYP2D6 are highly polymorphic and account together for about 40% of hepatic human phase I metabolism. These enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. CYP2C19 is a liver enzyme and is responsible for metabolizing a wide variety of drugs including the anticoagulant clopidogrel (Plavix), antiulcer drugs such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.

People who have reduced functioning of their CYP2C19 enzyme due to inactivating polymorphisms cannot effectively convert Plavix to its active form. As a result, Plavix may be less effective in altering platelet activity in those people. Those poor metabolizer patients may not receive the full benefit of Plavix treatment and may remain at risk for heart attack, stroke, and cardiovascular death. The polymorphism of the CYP2C19 enzyme results in poor, intermediate, moderate or rapid or extensive metabolizers of CYP2C19 drugs.

The CYP2C19 gene is mapped to chromosome 10q23.33 and encodes an enzyme of 490 amino acids. The CYP2C19*1 allele represents the wild-type allele. Considerable ethnic differences have been reported in the incidence of poor metabolizer (PM) genotypes of cytochrome P450 (CYP) 2C19. In poor metabolizers, two alleles are most frequently observed: a splice defect in exon 5 (CYP2C19*2; single base change G>A), and a premature stop codon at position 636 of exon 4 (CYP2C19*3; single base change G>A). The CYP2C19*2 polymorphism occurs almost exclusively in Caucasians; while the CYP2C19*3 polymorphism occurs in Asians. In general, rapid or extensive metabolizer with increased enzyme activity is used for *1/*1, intermediate metabolizer with moderate enzyme activity for *1/*2 and *1/*3, and poor metabolizer with reduced enzyme activity for *2/*2, *2/*3 and *3/*3.