Clinical Information

Primary metabolism of many drugs is performed by the cytochrome P450 (CYP) enzymes, a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues including the intestines and liver. One of these CYP enzymes, CYP2C19, participates in the metabolism of a wide variety of drugs, including the activation of the anticoagulant clopidogrel and the inactivation of citalopram.

CYP2C19 drug metabolism is variable among individuals. Some individuals have CYP2C19 genetic variants that lead to severely diminished or absent CYP2C19 catalytic activity (ie, poor metabolizers). The frequency of CYP2C19 variants (formerly known as polymorphisms) depends on ethnicity. CYP2C19 variants that produce poor metabolizers are found with frequencies of 2% to 5% in the White population, 4% in African Americans, 13% to 23% in Asians, and 38% to 79% in Polynesians and Micronesians.

The following table displays the CYP2C19 variants detected by this assay, the corresponding star allele, and the effect on CYP2C19 enzyme activity.

Table. Enzyme Activity of Individual Star Alleles

CYP2C19 drug metabolism is dependent on the specific genotype detected and also on the number and type of drugs administered to the patient. Phenotyping is derived from the Pharmacogene Variation Consortium website(1), the Clinical Pharmacogenetics Implementation Consortium website(2), published guidelines(3-8), and an exhaustive review of the CYP2C19 literature(9-10). Individuals without a detectable CYP2C19 variant will have the predicted phenotype of an extensive drug metabolizer and are designated as CYP2C19*1/*1. If an individual is homozygous or compound heterozygous for alleles with no activity, the individual is predicted to be a poor metabolizer. If an individual is heterozygous for an allele with no activity, the individual is predicted to be an intermediate metabolizer. Individuals with the CYP2C19*17 allele (in the absence of any inactive or decreased activity alleles) may have enhanced metabolism of drugs. In some cases, a range of potential phenotypes may be given, depending on the combination of alleles identified.

Patients who are poor metabolizers may benefit from dose alteration or selection of a comparable drug that is not primarily metabolized by CYP2C19. It is important to interpret the results of testing in the context of other coadministered drugs.