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Pharmacogenomic Testing

Pharmacogenomic Testing

Know the right drug and the right dosage before they take the medication

Predicting Patient Response
Predicting Patient Response
Research has demonstrated that genetic factors may profoundly influence a person’s response to medications, including possible side effects. Physicians are increasingly relying on pharmacogenomic testing to help personalize treatment by predicting patient response.
Advanced Sequencing
Advanced Sequencing

Exceltox’s advanced pharmacogenomic testing technology analyzes structural changes in a gene’s DNA sequence to assess the influence of a drug in a particular patient allowing physicians to understand if a patient could have a toxic reaction to a drug despite a low dosage, or if they will have any response at all, even at a high dosage.

Pain Management

Cytochrome P450 Enzymes

CYP450 enzymes are a group of proteins that help the body metabolize a wide variety of medications. Genetic variants shared by a large part of the human population of CYP450 alter the rate of drug metabolism – causing increased or decreased drug efficacy or adverse drug reactions.
Exceltox - Cytochrome P450 Enzymes
Exceltox - CYP2D6 and CYP3A4/5

CYP2D6 and CYP3A4/5

CYP2D6 and CYP3A4/5 are important enzymes within the Cytochrome P450 family, that are believed to metabolize ~30% of all pharmaceuticals.1 Both are critical in metabolizing many commonly prescribed opioids such as codeine, dihydrocodeine, oxycontin, and hydrocodone.

Characterizing Metabolic Types

There are four metabolic types associated with CYP450 gene variants:

  • Extensive Metabolizers (EM)
  • Poor Metabolizers (PM)
  • Intermediate Metabolizers (IM)
  • Ultra-rapid Metabolizers (UM)
Exceltox - Characterizing Metabolic Types

The Effects of CYP Variants on Therapeutic Efficacy

CYP Phenotype & Genotype
Active Drug

(inactivated by metabolism)

Prodrug

(needs metabolism to produce active drug)

Drug > Inactive Drug Prodrug > Inactive Drug
Ultra-rapid
  • Decreased eficacy
  • Active drug rapidly inactivated
  • Usually requires higher dose to offset inactivation
  • Increased eficacy
  • Rapid onset of effect
  • May require lower dose to prevent excessive accumulation of active drug
Extensive

 Normal Normal
Intermediate

 Normal Normal
Poor
  • Increased efficacy
  • Active metabolite may accumulate
  • Usually requires lower dose to avoid toxic accumulation
  • Decreased eficacy
  • Prodrug may accumulate
  • May require lower dose to avoid toxic accumulation or may require alternate drug

Mental Health

Neuroactive drugs (NAD’s) such as antidepressants, antipsychotics, and anxiolytics are important treatments for mental health. However, determining efficacy and appropriate dosage can be difficult, resulting in potentially negative outcomes:

Poor Drug Response
Exceltox - Poor Drug Response

Approximately 50% of all patients do not respond well enough to first line medication – requiring a time-consuming and exhaustive trial and error process to assess the optimal drug.

Prolonged Treatment
Exceltox - Prolonged Treatment

Treatment benefits can also take weeks to achieve, prolonging the trial and error process even further.

Adverse Side Effects
Exceltox - Adverse Side Effects

Patients may encounter adverse side effects with no benefits or face negative reactions with NAD’s interact with other prescription medications.

Cytochrome P450 Enzymes

CYP450 enzymes are a group of proteins that help the body metabolize a wide variety of foreign compounds.

Genetic variants of CYP450 alter the rate of drug metabolism – causing increased or decreased drug efficacy or adverse drug reactions.
Exceltox - Cytochrome P450 Enzymes
Exceltox - CYP2D6, CYP2C19, CYPA4, and CYP3A5

CYP2D6, CYP2C19, CYPA4, and CYP3A5

CYP2D6, CYP2C19, CYPA4, and CYP3A5 are part of the Cytochrome P450 family, and are responsible for metabolizing NAD’s. However, genetic variations of these CYP’s resulting in a spectrum of patient outcomes ranging from non-response to severe toxicity though prescribed an appropriate dose.

Neuroactive Drugs with Pharmacogenetic Information

Benefits

Pharmacogenetic testing for NAD’s can help physicians implement the appropriate drug and dosage.

Pharmacogenetic testing for NAD’s can help physicians implement the appropriate drug and dosage.

Determining the optimal drug early on can avoid an exhaustive, time-consuming process of treatment t…

Determining the optimal drug early on can avoid an exhaustive, time-consuming process of treatment trial and error that may have negative effects or no benefit at all.

Cytochrome P450 genotyping tests can be performed without taking patients off their medications.<sup…

Cytochrome P450 genotyping tests can be performed without taking patients off their medications.1

Testing information can be used as an adjunct to other tools for clearer guidance in selecting among…

Testing information can be used as an adjunct to other tools for clearer guidance in selecting among various therapeutic choices each patient.

Test Menu

Cytochrome P450 Enzymes

CYP2D6 and CYP3A4/5

Characterizing Metabolic Types

Extensive Metabolizers (EM)
Poor Metabolizers (PM)
Intermediate Metabolizers (IM)
Ultra-rapid Metabolizers (UM)
References
  1. Cytochrome P450 Enzyme Genotyping: Optimizing Patient Care Through Pharmacogenetics. Communiqué Mayo Reference Services. 2005. Sep. Vol 30, No. 9