About the AmpliChip® CYP450 Test

Introducing the AmpliChip CYP450 Test

The AmpliChip CYP450 Test is the first FDA-cleared test of its kind.

The AmpliChip CYP450 Test is intended to identify a patient's CYP2D6 and CYP2C19 genotype from genomic DNA extracted from a whole blood sample. This information can be used to aid clinicians in determining individualized dosing for therapeutics metabolized by the CYP2D6 or CYP2C19 genes, in order to improve patient outcomes by reducing adverse drug reactions and improving drug efficacy.

The AmpliChip CYP450 Test identifies a patient genotype and provides a predicted metabolic phenotype—poor, intermediate, extensive, or ultra-rapid metabolizer. With more than 15,000 different probes that allow identification of all the major CYP2D6 and CYP2C19 polymorphisms, including gene deletions and duplications, the AmpliChip CYP450 Test is highly specific, sensitive, and accurate.

Prescribing the AmpliChip CYP450 Test is simple. Once the laboratory receives a sample (whole blood), analysis of data can be achieved in approximately 8 hours, and test results can be available to doctors within several days in an easy-to-read printed report.

Individualizing Drug Therapy

Dosing issues can affect efficacy and drug safety. These three well-known tragic cases involved antidepressants or a common pain medication:

  • A 9-year-old died due to fluoxetine toxicity. Genetic tests confirmed that he had a gene defect at the CYP2D6 locus, which made him a poor metabolizer of fluoxetine (Sallee FR et al. J Child Adolesc Psychopharmacol. 2000;10:27-34)
  • A woman spent 10 years trying different treatments for depression and experiencing intolerable side effects from all medications, until she was switched to a drug that did not need the CYP2D6 enzyme to function (Lerner B et al. J Genet Couns. 2004;13:259-266)
  • In another case, the problem was not that the patient was a poor metabolizer but that she was an ultra-rapid metabolizer. In 2006, The Lancet described the death of a nursing infant whose mother was prescribed acetaminophen with codeine, a pro-drug, for episiotomy pain. (Koren et al. “Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother.” Lancet. 2006; 368: 704) Usually, an ultra-rapid metabolizer breaks down a drug so quickly that the drug has little or no effect. In the case of a pro-drug, the expected effect is the opposite and can lead to an overdose.

In these cases, patients were either poor or ultra-rapid metabolizers of CYP2D6. These cases are unique in their severity, but many medications can be difficult to dose because of genetic variations in the genes that influence metabolism.

Clinical Validity of CYP450 Genotyping

  • Adjustment of drug dosage could be beneficial particularly for individuals possessing the poor and ultra-rapid metabolizer phenotypes.
  • Intermediate metabolizers have also been shown to respond differently to certain drugs.
  • These measures may improve patient outcome by reducing adverse drug reactions and improving drug efficacy .
  • Dosage adjustment for antidepressants and antipsychotics have been proposed.

Genotype, Metabolic Phenotypes, and Drug Metabolism

Genetic variations of CYP450 enzyme activity are expressed as four predicted phenotypes. An estimated 30% to 60% of patients do not respond to medication. This is both troubling from a clinical standpoint, because the patient doesn't feel better, and from a cost standpoint, as the therapy is ineffective. Although these cases of nonresponse and adverse reactions are not always linked to phenotype, they can be.

Interpatient variations of CYP2D6 enzyme activity are expressed as four predicted phenotypes based on pharmacogenetic analyses:

Impact of Phenotype on Drug Metabolism

Demographics and Prevalence

Although patients can generally be classified into one of the four phenotypic groups, there is pronounced racial and geographic variability, with some polymorphisms and alleles found in virtually only one racial population. Approximately 7% of Caucasians are poor metabolizers of CYP2D6, whereas only about 1% to 2% of Asian and 2% to 4% of African American populations are in that same category. There is a 50% prevalence of several reduced-activity alleles in Asians and a 30% prevalence in certain African populations that lead to a higher percentage of intermediate metabolizers with low enzyme activity. Although the extreme activities of the poor and ultra-rapid metabolizer phenotypes have the greatest potential effect on individual drug response, intermediate metabolizers have also been shown to respond differently to certain drugs.

Population Differences

Relevant Information. Reliable Results.

The AmpliChip CYP450 Test has an overall accuracy of greater than 99% for detection and genotype call rate and only needs to be given to a patient once in a lifetime. However, the interpretation of the test result may change throughout a patient's life depending on age, medications, and other factors, and should be reviewed as appropriate by a healthcare professional.

This study by Bradford shows the prevalence of polymorphisms for CYP2D6. A more comprehensive table is available in the AmpliChip CYP450 Test package insert.

While some polymorphisms may be rare in the overall population, they may be more frequent in a subgroup. For example, *17 is rare among Caucasians, but frequent among Black Americans and Black Africans. *10 is extremely common in Chinese and Japanese populations, while less frequent with Caucasian, Black African, and Black American groups. *41 is very frequent among Caucasian Europeans, but there are no data on prevalence for other populations.

The AmpliChip CYP450 Test detects 27 genetic variations of CYP2D6. Such a broad coverage of CYP2D6 makes the test relevant across a diverse patient base. Unlike many other tests, the AmpliChip CYP450 Test automatically checks that duplications of genes are functional, a feature that helps the resulting accuracy. Without such a feature, a test can wrongly classify a patient as an ultra-rapid metabolizer.