Pharmacogenetics of Pain
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Activation of Common Analgesics by CYP 2D6

Pharmacogenetic Effect of
Cytochrome Genotypes

A. PM poor metabolizer, absent or greatly reduced ability to clear or activate drugs.
B. IM intermediate metabolizer. Heterozygotes for normal and reduced activity genes.
C. EM extensive metabolizer. The norm.
D. UM Ultra Metabolizer. Greatly increased activity accelerating clearance or activation

Population Frequency of Cytochrome p450 (CYP) genotypes

Currently Available Tests

Individualized Patient Reports based on patient drug, herbal and diet regimens

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Currently Available Tests
CYP2D6 (cytochrome P450 2D6) is the best studied of the DMEs and acts on one-fourth of all prescription drugs, including the selective serotonin reuptake inhibitors (SSRI), tricylic antidepressants (TCA), betablockers such as Inderal and the Type 1A antiarrhythmics. Approximately 10% of the population has a slow acting form of this enzyme and 7% a super-fast acting form. Thirty-five percent are carriers of a non-functional 2D6 allele, especially elevating the risk of ADRs when these individuals are taking multiple drugs. Drugs that CYP2D6 metabolizes include Prozac, Zoloft, Paxil, Effexor, hydrocodone , amitriptyline, Claritin, cyclobenzaprine, Haldol, metoprolol, Rythmol, Tagamet, tamoxifen, and the over-the-counter diphenylhydramine drugs, Allegra, Dytuss, and Tusstat. CYP2D6 is responsible for activating the pro-drug codeine into its active form and the drug is therefore inactive in CYP2D6 slow metabolizers.

CYP2C9 (cytochrome P450 2C9) is the primary route of metabolism for Coumadin (warfarin) and Dilantin (phenytoin). Approximately 10% of the population are carriers of at least one allele for the slow-metabolizing form of CYP2C9 and may be treatable with 50% of the dose at which normal metabolizers are treated. Other drugs metabolized by CYP2C9 include Amaryl, isoniazid, sulfa, ibuprofen, amitriptyline, Hyzaar, THC (tetrahydrocannabinol), naproxen, and Viagra.

CYP2C19 (cytochrome P450 2C19) is associated with the metabolism of carisoprodol, diazepam, Dilantin, Premarin, and Prevacid.

CYP1A2 (cytochrome P450 1A2) is associated with the metabolism of amitriptyline, olanzapine, haloperidol, duloxetine, propranolol, theophylline, caffeine, diazepam, chlordiazepoxide, estrogens, tamoxifen, and cyclobenzaprine.

NAT2 (N-acetyltransferase 2) is a second-step DME that acts on isoniazid, procainamide, and Azulfidine. The frequency of the NAT2 "slow acetylator" in various worldwide populations ranges from 10% to more than 90%.

Individualized Patient Reports based on patient drug, herbal and diet regimens

DNA test reports can include patient specific information on potential drug-drug interactions (DDIs) mediated by the tested polymorphic drug metabolizing enzymes, taking into account patient diet, over the counter medicines, herbal preparations drugs of abuse and other factors. Testing patients for drug metabolizing enzyme genotypes can provide physicians with immediate insight into common individual differences in their patients' drug processing ability and helps the physician more quickly improve the efficacy and safety of the prescribed treatments. This information will be especially valuable when potential drug-drug interactions (DDIs) are a possibility.


Ordering Tests
Now you can add another dimension to providing safer and more efficacious care to your patients by ordering DNA Drug Reaction Profiles for them. Each pharmacogenetic test is only $250.00, $600 for a standard panel that includes 2D6, 2C9, and 2C19, or $1000 for all five. Five-day stat testing is available for an additional $100. The process couldn't be simpler, we provide you with a cheek swab collection kit and prepaid shipping to return samples to our laboratory. Call 800 523-3080 for more information or to obtain collection kits.