CYTOCHROME P450 2C19 PROTEIN (HUMAN)

The CYP2C9 and CYP2C19 are the main isoforms for the metabolism of the antiseizure drug phenytoin and for the anticoagulant S-warfarin. Although CYP2C19 metabolizes fewer drugs than CYP2D6 does, the drugs CYP2C19 does metabolize are clinically important (Table 10.6). Deficit of CYP2C19 is found in the PM phenotype, which is only seen in 8 to 13% of Caucasians, 20 to 30% of the Asian population (11–23% of Japanese and 5–37% of Chinese), up to 20% of the black African-American population, 14 to 15% of Saudi Arabians and Ethiopians, and up to 70% of Pacific Islanders. The more common mutant allele in these individuals is CYP2C19*2, which expresses an inactive enzyme. The large interindividual variability observed in the therapeutic response to the antiseizure drug mephenytoin is attributed to CYP2C19 polymorphism, which catalyzes the p-hydroxylation of its S-stereoisomer. The R-enantiomer is N-demethylated by CYP2C8 with no difference in its metabolism between PMs and EMs.