Sorted By Test Name - Mayo Medical Laboratories

3A4B
61241
CYP2D6: -Alprenolol -Amitriptyline -Amphetamine -Aripiprazole -Atomoxetine -Bufuradol -Carvedilol
-Chlorpheniramine -Chlorpromazine -Clomipramine -Codeine -Debrisoquine -Desipramine
-Dextromethorphan -Dexfenfluramine -Diltiazem -Disopyramide -Donepezil -Duloxetine -Encainide
-Flecainide -Fluoxetine -Fluvoxamine -Haloperidol -Iloperidone -Imipramine -Labetalol -Lidocaine
-Metoclopramide -Methoxyamphetamine -Metoprolol -Mexilitine -Minaprine -Mirtazapine -Nebivolol
-Nortriptyline -Oxycodone -Ondansetron -Paroxetene -Pergolide -Perhexiline -Perphenazine
-Promethazine -Phenformin -Pimozide -Propafenone -Propranolol -Respirdone -Sertraline -Sparteine
-Tamoxifen -Thioridazine -Tegaserod -Timolol -Tramadol -Venlafaxine -Zuclopenthixol
Coadministration may decrease the rate of elimination of other drugs metabolized by of CYP2D6.
Drug-drug interactions and drug-metabolite inhibition or activation must be considered when dealing with
heterozygous individuals. Drug-metabolite inhibition occurs frequently with selective serotonin reuptake
inhibitors and tricyclic antidepressants, resulting in inhibition of residual functional CYP2D6 catalytic
activity. Each report will include a list of commonly prescribed drugs, by drug class, that are known to
alter CYP2D6 activity. This list includes only those drugs for which established, peer-reviewed literature
substantiates the effect. The list provided is not all-inclusive. CYP2D6 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 renal and hepatic function and age.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Bertilsson L, Dahl ML, Dalen P, Al-Shurbaji A: Molecular genetics of
CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol 2002
Feb;53(2):111-122 2. Lundqvist E, Johansson I, Ingelman-Sundberg M: Genetic mechanisms for
duplication and multiduplication of the human CYP2D6 gene and methods for detection of duplicated
CYP2D6 genes. Gene 1999 Jan 21;226(2):327-338 3. Kirchheiner J, Brosen K, Dahl ML, et al: CYP2D6
and CYPSC19 genotype-based dose recommendations for antidepressants: a first step towards
subpopulation-specific dosages. Acta Psych Scand 2001 Sept;104(3):173-192 4. Lam YWF, Gaedigk A,
Ereshefsy L, et al: CYP2D6 inhibition by selective serotonin reuptake inhibitors: analysis of achievable
steady-state plasma concentrations and the effect of ultrarapid metabolism at CYP2D6. Pharmacotherapy
2002;22:1001-1006
Cytochrome P450 3A4 Genotype, Blood
Clinical Information: The cytochrome P450 (CYP) 3A4 enzyme is responsible for the metabolism of
approximately 50% of drugs that undergo hepatic metabolism and first pass metabolism in intestinal
epithelial cells, including lipid-lowering drugs. The CYP3A4 enzyme activity is highly variable.(1) While
polymorphisms and mutations have been described for the CYP3A4 gene, they do not explain the highly
variable enzymatic activity of the encoded protein.(2) A CYP3A4 (c522-191C->T) intron 6
polymorphism (CYP3A4*22) affects hepatic expression of CYP3A4 and response to statin drugs. The
CYP3A4*22 allele is associated with reduced CYP3A4 activity, resulting in a better response to
lipid-lowering drugs, such as simvastatin, atorvastatin, or lovastatin. Studies show that CYP3A4 mRNA
level and enzyme activity in the liver with CC genotype were 1.7- and 2.5-fold greater than in CT and TT
carriers, respectively. In 235 patients taking stable doses of drugs for lipid control, carriers of the T allele
required significantly lower statin doses for optimal lipid control than did non-T carriers.(3) These results
indicate that CYP3A4*22 markedly affects expression of CYP3A4 and could serve as a biomarker for
CYP3A4 metabolizer phenotype. The reported allele frequency of CYP3A4*22 in Caucasians was 5% to
8%. The allele frequency is 4.3% in African Americans and in Chinese.
Useful For: An aid to clinicians in determining therapeutic strategies for drugs that are metabolized by
CYP3A4, including atorvastatin, simvastatin and lovastatin
Interpretation: CC Detected: The CYP3A4 *22 (c.522-191C->T) allele was not identified (ie, CC
genotype detected) in this individual. This genotype predicts higher CYP3A4 enzyme activity. Individuals
with this genotype may require higher statin doses for optimal therapy. CT Detected: This individual is
heterozygous (CT) for the CYP3A4*22 (c.522-191C->T) allele. This genotype predicts lower CYP3A4
enzyme activity. Individuals with this genotype may require lower statin doses. TT Detected: This
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