Sorted By Test Name - Mayo Medical Laboratories

drugs and environmental factors.
Useful For: Identifying patients who are poor, intermediate, extensive, or ultrarapid metabolizers of
drugs metabolized by CYP1A2 Adjusting dosages for drugs that are metabolized by CYP1A2
Interpretation: An interpretive report will be provided that includes assay information, genotype, and
an interpretation indicating whether results are consistent with a poor, intermediate, extensive, or
ultra-rapid metabolizer phenotype. The report will list drugs known to affect metabolism by CYP1A2.
Direct polymorphism analysis for -3860G->A, -2467T->del T, -729C->T, -163C->A, 125C->G,
558C->A, 2385G->A, 2473G->A, 2499A->T, 3497G->A, 3533G->A, 5090C->T, or 5166G->A is
performed following PCR amplification. Direct DNA testing will not detect all the known mutations that
result in decreased or inactive CYP1A2 alleles. This assay does not test for some known polymorphisms
because those polymorphisms have not been associated with alterations in enzymatic activity. Rare or
undescribed variants may not have been found during validation but will be sequence verified upon
detection. See http:///www.cypalleles.ki.se/cyp1a2.html for a full description of CYP1A2 alleles. Absence
of a detectable gene mutation or polymorphism does not rule out the possibility that a patient has a
metabolizer status other than predicted above. The frequency of polymorphisms causing poor metabolism
has not been fully characterized in various ethnic groups. Patients with an ultrarapid, extensive, or
intermediate genotype may have CYP1A2 enzyme activity inhibited or induced by a variety of
substances, medications, or their metabolites. The following is a listing of substances known 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, and 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, and 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, and 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, et 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
Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 572