AmpliChip™ CYP450
Overview
Cytochrome P450 enzymes affect the metabolism of
nearly half of the drugs used today. Genetic variations
(polymorphisms) in the CYP450 enzymes result in
abnormal drug metabolism which can lead to adverse
drug reactions or suboptimal therapeutic response.
The AmpliChip™ is the first FDA-cleared
microarray assay to identify an individual’s genetic
variation in two critical drug metabolism genes,
CYP2D6 and CYP2C19. These cytochrome P450
genes play a major role in the metabolism of many
widely prescribed drugs, including anti-depressants,
anti-psychotics,
anti-epileptics,
proton
pump
inhibitors, and beta-blockers.
Identification of patient CYP2D6 and CYP2C19
genotypes can help predict expected enzyme activity
allowing clinicians to individualize drug treatment for
each patient.
Individualized therapy may assist
patients by reducing adverse drug reactions and
minimizing drug dose requirements.
Mutation analysis provides a simple and reliable
method for identifying at-risk patients who may
benefit from drug dosage reduction to avoid adverse
reactions or modifying dosage to optimize therapeutic
efficacy.
CYP2D6 & CYP2C19
The cytochrome P450 isoenzymes encoded by the
CYP2D6 and CYP2C19 genes are responsible for the
metabolism of a large number of widely prescribed
drugs (Tables 1 and 2). These genes are polymorphic,
with allelic variation significantly affecting drug
metabolism. Certain allelic variants exhibit either
altered activity or complete absence of enzymatic
activity.1 The CYP2D6 gene has at least 70 allelic
variants resulting in four phenotypic types: poor
metabolizers with gene inactivation of both alleles,
intermediate metabolizers with one reduced activity
allele and one null allele, extensive metabolizers with
at least one functional allele, and ultra-rapid
metabolizers with excess enzymatic activity due to
multiple copies of functional alleles from gene
duplication. The CYP2C19 gene has two major variant
alleles that result in enzyme deficiency. The
AmpliChip™ detects 29 polymorphisms in the 2D6 and
2 polymorphisms in the 2C19 gene, as well as gene
duplications and deletions
Due to the impact of these polymorphisms upon the
pharmacokinetics of antidepressants and antipsychotics, as well as the metabolism of active
metabolites, distinct CYP2D6 and CYP2C19
genotype-based dose recommendations have been
proposed to improve patient outcomes.2,3 Identification
of patient CYP2D6 and CYP2C19 genotypes can help
predict expected drug metabolism enzyme activity
allowing clinicians to individualize drug treatment for
each patient. Individualized therapy may assist patients
by reducing adverse drug reactions and minimizing
drug dose requirements.
Other Factors Affecting Metabolism
Besides polymorphisms, other factors can influence
drug interactions via affecting expression of the CYP
proteins, including age, gender, hormones, hepatic
disease, inflammation, nutrition, pregnancy and
environmental factors.4
Clinical Utility
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•
•
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FDA-cleared for diagnostic analysis of two critical drug metabolism genes: CYP2D6 and CYP2C19
Identifies poor metabolizers prior to therapy to help avoid adverse drug reactions
Identifies ultra-rapid and intermediate metabolizers for pre-therapeutic drug adjustment to maximize drug efficacy
Approximately 10% of Caucasians are poor metabolizers, 35% intermediate, 48% extensive and 7% ultra-rapid5
Ordering Information & Specimen Requirements
Test Code Test Name
4565
AmpliChip™ CYP450
(CYP2D6, CYP2C19)
Specimen Requirements
5 (3) mL Whole Blood EDTA; Ambient or Refrigerated. Ship immediately by
overnight courier.
©2006 Specialty Laboratories
AmpliChip 3/06 TN1221
27027 Tourney Road, Valencia, CA 91355 • Phone 800-421-7110 • Fax 661-799-6634 • www.specialtylabs.com
Methodology
Affymetrix
References
1.
2.
3.
Daly AK. Pharmacogenetics of the major polymorphic
metabolizing enzymes. Fundam Clin Pharmacol
2003;17:27-41.
Brockmöller J, Kirchheiner J, Schmider J, et al. The
impact of the CYP2D6 polymorphism on haloperidol
pharmacokinetics and on the outcome of haloperidol
treatment. Clin Pharmacol Ther 2002;72:438-52.
Kirchheiner J, Brøsen K, Dahl ML, et al. CYP2D6 and
CYP2C19 genotype-based dose recommendations for
antidepressants: a first step towards subpopulationspecific dosages. Acta Psychiatr Scand 2001;104:17392.
4.
5.
6.
7.
Badyal DK, Dadhich AP. Cytochrome P450 and drug
interactions. Indian J Pharmacol 2001;33:248-59.
Available at: http://www.pgxlab.com. Accessed
September 14, 2005.
Kirchheiner J, Nickchen K, Bauer M, et al.
Pharmacogenetics
of
antidepressants
and
antipsychotics: the contribution of allelic variations to
the phenotype of drug response. Mol Psychiatry
2004;9:442-73.
AmpliChip™ CYP450 Package Insert, Roche
Diagnostics, Inc., 2005.
Table 1. Drugs metabolized by CYP2D6
Carvedilol, Metoprolol, Propafenone and Timolol
Beta Blockers
Anti-depressants Amitriptyline, Clomipramine, Desipramine, Paroxetine,
Imipramine and Venlafaxine
Haloperidol, Risperidone and Thioridazine
Anti-psychotics
Atomoxetine, Ondansetron, Dextromethorphan, Tamoxifen,
Others
Flecainide, Mexiletine, Codeine and Tramadol
Table 2. Drugs metabolized by CYP2C19
Omeprazole, Lansoprazole and Pantoprazole
Proton Pump Inhibitors
Diazepam, Phenytoin and Phenobarbitone
Anti-epileptics
Amitriptyline, Clomipramine, Cyclophosphamide,
Others
Progesterone
Other useful Web sites:
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www.pgxlabs.com.
www.geneMedRx.com.
www.imm.ki.se/CYPalleles
For complete information please visit our Web site at www.specialtylabs.com or
call Client Services at 800-421-4449.
©2006 Specialty Laboratories
AmpliChip 3/06 TN1221
27027 Tourney Road, Valencia, CA 91355 • Phone 800-421-7110 • Fax 661-799-6634 • www.specialtylabs.com