Sorted By Test Name - Mayo Medical Laboratories

2C19O
60335
without inactivating polymorphisms have the phenotype of an extensive drug metabolizer and are
designated as CYP2C19*1. All of the identified polymorphisms are autosomal recessive. Consequently,
only individuals who are homozygous or who are compound heterozygous for these polymorphisms are
poor metabolizers. Individuals who are heterozygous, with 1 normal gene and 1 polymorphic gene, will
have metabolism intermediate between the extensive (normal) and poor metabolizers. Individuals
receiving clopidogrel who are carriers (heterozygous) or homozygous for the CYP2C19 polymorphisms
detected by this test will likely require a dose increase to achieve effective inhibition of platelet
aggregation. Dosing of drugs that are metabolized through CYP2C19 may require adjustment for the
individual patient. Patients who are poor metabolizers may benefit by dose alteration or by being switched
to other comparable drugs that are not metabolized primarily by CYP2C19. CYP2C19 poor metabolizers
may fail to activate clopidogrel, a prodrug. Consideration of increased dosing or alternative anticoagulant
is suggested. The following is a partial listing of drugs known to affect CYP2C19 activity as of the date of
this report. Drugs that undergo metabolism by CYP2C19: -Anticoagulants: clopidogrel (Plavix)
-Anticonvulsants: mephenytoin, diazepam, phenytoin, primidone -Antidepressants: amitriptyline,
citalopram, S-citalopram, clomipramine -Antineoplastics: cyclophosphamide -Antiretrovirals: nelfinavir
-Proton pump inhibitors: lansoprazole, omeprazole, pantoprazole -Miscellaneous drugs: progesterone,
propranolol, R-warfarin (less active isomer), proguanil, diazepam Coadministration may decrease the rate
of elimination of other drugs metabolized by CYP2C19 Drugs known to increase CYP2C19 activity:
-Carbamazepine, prednisone, rifampin Coadministration of these drugs increase synthesis of CYP2C19
and increase the rate of elimination of drugs metabolized by CYP2C19 Drugs known to decrease
CYP2C19 activity: -Chloramphenicol, cimetidine, felbamate, fluoxetine, fluvoxamine, indomethacin,
ketoconazole, lansoprazole, modafinil, omeprazole, probenecid, ticlopidine, topiramate Coadministration
will decrease the rate of metabolism of CYP2C19 metabolized drugs, increasing the possibility of
toxicity, particularly in heterozygous individuals
Useful For: Identifying patients who are poor metabolizers or extensive metabolizers of drugs that are
modified by CYP2C19 Individuals who have resistance to anticoagulation with clopidogrel
Interpretation: An interpretive report will be provided. The normal genotype for CYP2C19 is
CYP2C19*1. Other genotypes that lead to inactive or reduced activity alleles include CYP2C19*2,
CYP2C19*3, CYP2C19*4, CYP2C19*6, CYP2C19*7, and CYP2C19*8. An individual who is
homozygous wild type, or CYP2C19*1/CYP2C19*1, is considered an extensive metabolizer. An
individual who is heterozygous for the wild type and variant genotype is considered an intermediate
metabolizer. An individual who is either a homozygous variant or compound heterozygous variant
genotype is considered a poor metabolizer. Individuals who are homozygous for *1 but who also have the
CYP2C19*17 promoter polymorphism may have enhanced metabolism of drugs, and may require higher
drug doses to maintain therapeutic effectiveness. Individuals with a *17 allele may activate prodrugs, such
as clopidogrel, to the active metabolites to a greater extent than extensive metabolizers. Drug-drug
interactions and drug/metabolite inhibition must be considered when dealing with heterozygous
individuals. Drug/metabolite inhibition can occur, resulting in inhibition of residual functional CYP2C19
catalytic activity. Patients may also develop toxicity problems if liver and kidney functions are impaired.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Blaisdell J, Mohrenweiser H, Jackson J, et al: Identification and functional
characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics 2002
Dec;12(9):703-711 2. Jeppesen U, Gram LF, Vistisen K, Loft S, et al: Dose-dependent inhibition of
CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine. Eur J Clin
Pharmacol 1996;51(1):73-78 3. Simon T, Verstuyft C, Mary-Krause M, et al: Genetic determinants
response to clopidogrel and cardiovascular events. N Engl J Med 2009;360(4):363-375 4. Mega J, Close
S, Wiviott D, et al: Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med
2009;360:354-362
Cytochrome P450 2C19 Genotype by Sequence Analysis, Saliva
Clinical Information: Primary metabolism of many drugs is performed by cytochrome P450
(CYP450), a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues
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