Cytochrome P450 2D6/2C19 Genotyping

Cytochrome P450 2D6 (CYP2D6) is a drug-metabolizing enzyme involved in the metabolism of more than 65 clinically important drugs including some antidepressants, anti-psychotics, opioids, beta-blockers, antiemetics, atomoxetine and tamoxifen. Individuals with some variant CYP2D6 alleles may experience a reduced therapeutic response and may be at risk for side effects from drugs that are metabolized by CYP2D6. CYP2D6 genotype information can be utilized to predict CYP2D6 metabolic phenotype, which can be used as an aid in determining a therapeutic strategy for drugs that are metabolized by CYP2D6. For example, CYP2D6 ultrarapid metabolizers may experience exaggerated side effects after the administration of codeine, while poor metabolizers may experience a reduced analgesic effect due to insufficient biotransformation into morphine. In these instances, alternative drugs may be considered.

Variation in the CYP2D6 gene can result in ultrarapid (UM), normal (NM), intermediate (IM) and poor (PM) drug-metabolizing phenotypes. Depending upon the genotype, a range between some of these phenotypes may be predicted by this assay. In general, relative to the *1 allele (normal function), *2, *35 and *53 alleles have normal function. *9, *10, *14, *17, *29, *41, *49 and *59 alleles have decreased function, while *3, *4, *5, *6, *7, *8, *11, *12, *13, *15, *31, *36, *40, *42 and *68 alleles have no function.

Cytochrome P450 2C19 (CYP2C19) is a drug-metabolizing enzyme involved in the metabolism of several clinically important drugs including the platelet aggregation inhibitor clopidogrel, the tricyclic antidepressants amitriptyline and nortriptyline, and the selective serotonin reuptake inhibitors citalopram and sertraline, and some proton pump inhibitors including omeprazole and pantoprazole. Individuals with some variant CYP2C19 alleles may experience a reduced therapeutic response and may be at risk for side effects from drugs that are metabolized by CPY2C19. CYP2C19 genotype information can be utilized to predict CYP2C19 metabolic phenotype, which can be used as an aid in determining a therapeutic strategy for drugs that are metabolized by CYP2C19. For example, the use of clopidogrel with an intermediate or poor metabolizer is associated with reduced platelet inhibition and an increased risk of cardiovascular complications, such as myocardial infarction, stroke, stent thrombosis and/or death, as compared with normal metabolizers. Ultrarapid metabolism is associated with an enhanced response to clopidogrel and increased risk of bleeding. In these instances, alternative drugs may be considered.

Variation in the CYP2C19 gene can result in ultrarapid (UM), rapid (RM), normal (NM), intermediate (IM), likely intermediate (LIM), poor (PM) and likely poor (LPM) drug-metabolizing phenotypes. In general, relative to the *1 allele (normal function), the *17 allele has increased function, *9 and *10 alleles have decreased function, while *2, *3, *4, *5, *6, *7, *8 and *35 alleles have no function.