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Address
304 North Cardinal St.
Dorchester Center, MA 02124
Work Hours
Monday to Friday: 7AM - 7PM
Weekend: 10AM - 5PM
Cytochrome P450 2D6 (CYP2D6) is an isoenzyme of the CYP450 superfamily and is involved in the metabolism of up to 25% of commonly prescribed drugs, including beta blockers and many pain medications. The genetically determined CYP2D6 metabolizer status may affect the specific drug and its dose that is most effective for each patient. The CYP2D6 metabolizer status may cause toxicity because it increases effective drug concentration, or conversely may decrease effective drug concentration and thus cause therapeutic failure. Similarly the CYP2D6 metabolizer status affects the efficacy or toxicity of prodrugs that require conversion to active drug by CYP2D6.
Beta blockers are a class of drugs that are used to prevent cardiac arrhythmias, second heart attack and for management of angina pectoris. Beta blockers, as the name suggests, act by inhibiting the beta adrenergic receptors on cardiac muscles. Many beta blockers are metabolized by CYP2D6, and a few beta blockers are administered as prodrugs that are converted to active drug by CYP2D6. The CYP2D6 metabolizer status should be considered when determining the choice and dose of beta blocker medications that will be most effective and safe for each patient.
A number of pain medications are metabolized by CYP2D6, and many other pain medications, including opiates, are prodrugs that are activated by CYP2D6. As described previously, genetically determined CYP2D6 metabolizer status may affect the drug choice and dose of pain medications that are either metabolized by CYP2D6 (lidocaine), or are prodrugs converted to active drug by CYP2D6 (dihydrocodeine, codeine, hydrocodone, oxycodone, tramadol, amitryiptylene).
It is also important to note that a number of drugs are known to inhibit CYP2D6 enzyme activity. Co-administration of CYP2D6 inhibitors should be monitored because they may affect CYP2D metabolizer status, and thus affect choice of drug and its dose for each patient to maximize efficacy and minimize toxicity.
The CYP2D6 gene is located on the long arm of chromosome 22 at position 13.1. More precisely it is located from base pair 42,126,498 to 42,130,880 on chromosome 22. Over 50 allelic variants of CYP2D6 have been identified. Alleles that are most common or cause significant effects in CYP2D6 enzyme activity are: *1, *3, *4, *5, *6, *9, *10, *17. The *5 allele is a gene deletion.
These assays were developed using CLSI guidelines. Control DNA samples of known genotype are tested together with each patient sample to ensure correct results. Genomic DNA is extracted from the submitted buccal swab sample and subjected to real time polymerase chain reaction (real time PCR). Detection of specific single nucleotide polymorphisms (SNPs), or determination of gene deletion, was used to determine the genotype. The following CYP2D6 alleles were tested: *3, *4, *5, *6, *9, *10, and *17. The wild type or normal allele (*1) was assigned by default if none of the variant alleles were detected.
i. Physical damage
ii. Specimen appears to have microbial contamination or other visible contamination
iii. The name on the tube does not match the name on the paperwork.
iv. It is older than 10 days.
There are 4 phenotypic categories for CYP2D6: Normal (extensive) Metabolizer, Normal – Intermediate Metabolizer, Intermediate Metabolizer and Poor Metabolizer.
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The detection of genetic variants does not replace the need for therapeutic drug monitoring or other appropriate clinical monitoring by the health care provider. Additional rare mutations for the CYP2D6 gene that are not described in the methodology section will not be detected. CYP2D6 metabolism is also influenced by concomitant medications, inhibitors, diet and various disease states. These tests were developed and the performance characteristics were determined by MDL. The CYP2D6 test has not been cleared or approved by the US Food and Drug Administration. The FDA has determined that such approval is not necessary.
This test is approved for use on New York state residents.
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