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2C19S
60439
to affect CYP1A2 activity as the date of this report. Drugs and substances known to increase (induce)
CYP1A2 activity include: -Broccoli, brussel sprouts, char-grilled meat, insulin, methylcholanthrene,
modafinil, nafcillin, beta-naphthoflavone, omeprazole, tobacco Coadministration will increase the rate
of metabolism of CYP1A2-metabolized drugs and may change the effectiveness of the drug. Drugs and
substances known to decrease CYP1A2 activity include: -Amiodarone, cimetidine, ciprofloxacin,
fluoroquinolones, fluvoxamine, furafylline, interferon, methoxsalen, mibefradil Coadministration will
decrease the rate of metabolism of CYP1A2-metabolized drugs, increasing the possibility of toxicity.
Drugs and substances that undergo metabolism by CYP1A2 include: -Acetaminophen, amitriptyline,
caffeine, clomipramine, clozapine, cyclobenzaprine, estradiol, fluvoxamine, haloperidol, imipramine,
mexiletine, naproxen, olanzapine, ondansetron, phenacetin, propranolol, riluzole, ropivacaine, tacrine,
theophylline, tizanidine, verapamil, (R)warfarin, zileuton, zolmitriptan Coadministration may decrease
the rate of elimination of other drugs metabolized by CYP1A2. Drug-drug interactions and
drug-metabolite inhibition or induction must be considered when dealing with heterozygous individuals.
Drug-metabolite inhibition occurs with the drugs noted above resulting in inhibition of residual
functional CYP1A2 catalytic activity. Drug-metabolite induction occurs with the drugs noted above
resulting in variable increase in CYP1A2 enzyme function. This inducibility is under genetic control
and this is further varies per ethnicity. Each report will include a list of commonly prescribed drugs that
are known to alter CYP1A2 activity. This list includes only those drugs for which established,
peer-reviewed literature substantiates the effect. The list provided may not be all-inclusive. CYP1A2
activity also is dependent upon hepatic and renal function status, as well as age. Patients also may
develop toxicity if hepatic or renal function is decreased. Drug metabolism also is known to decrease
with age. It is important to interpret the results of testing and dose adjustments in the context of hepatic
and renal function and age.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Shirley KL, Hon YY, Penzak SR, et al: Correlation of cytochrome P450
(CYP) 1A2 activity using caffeine phenotyping and olanzapine disposition in healthy volunteers.
Neuropsychopharmacology, 2003;28(5):961-966 2. Shimoda K, Someya T, Morita S, et al: Lack of
impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A
polymorphism at position -2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of
haloperidol in smoking male Japanese with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry
2002;26(2):261-265 3. Obase Y, Shimoda T, Kawano T, at al: Polymorphisms in the CYP1A2 gene and
theophylline metabolism in patients with asthma. Clin Pharmacol Ther 2003;73(5):468-474 4. Cornelis
MC, El-Sohemy A, Kabagambe EK, et al: CYP1A2 genotype, and risk of myocardial infarction. JAMA
2006 Aug 16; 296(7):764-765
Cytochrome P450 2C19 Genotype by Sequence Analysis
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
including the intestines and liver. One of these CYP450 enzymes, CYP2C19, metabolizes a wide variety
of drugs including antiulcer drugs such as omeprazole, antiseizure drugs such as mephenytoin, the
antimalarial proguanil, and the anxiolytic diazepam. It is also partially responsible for metabolizing other
drugs such as the beta-blocker propranolol and the antidepressants fluvoxamine and fluoxetine. It is also
involved in the activation of the anticoagulant clopidogrel. CYP2C19 drug metabolism is variable. Some
individuals have altered CYP2C19 gene sequences that result in synthesis of enzyme devoid of catalytic
activity or in enzyme with diminished catalytic activity. These individuals metabolize clopidogrel,
mephenytoin, omeprazole, diazepam, proguanil, and propranolol poorly. A number of specific
polymorphisms have been found in the CYP2C19 gene that result in enzymatic deficiencies. The
frequency of these polymorphisms varies within the major ethnic groups. CYP2C19 polymorphisms that
produce poor metabolizers are found with frequencies of 2% to 5% in Caucasians, 4% in African
Americans, 13% to 23% in Asians, and 38% to 79% in Polynesians and Micronesians. The following
information outlines the relationship between the polymorphisms detected in the assay and the effect on
the enzyme activity encoded by that allele: CYP2C19 Allele Nucleotide Change Effect on Enzyme
Metabolism *1 None (wild type) Extensive metabolizer (normal) *2 c.681G->A No activity *3
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