Know the right drug and the right dosage before they take the medication.
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.
PGx Testing
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.
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.
CYP2D6 and CYP3A4
CYP2D6 and CYP3A4 are important enzymes within the Cytochrome P450 family, that are believed to metabolize ~30% of all pharmaceuticals. 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)
The Effects of CYP Variants on Therapeutic Efficacy
CYP Phenotype & Genotype:ULTRA-RAPID
Active Drug:
Inactivated by metabolism
[ Drug > Inactive Drug ]
- Decreased efficacy
- Active drug rapidly inactivated
- Usually requires higher dose to offset inactivation
Prodrug:
Needs metabolism to produce active drug
[ Prodrug > Inactive Drug ]
- Increased efficacy
- Rapid onset of effect
- May require lower dose to prevent excessive accumulation of active drug
CYP Phenotype & Genotype:EXTENSIVE
Active Drug:
Inactivated by metabolism
[ Drug > Inactive Drug ]
- Normal
Prodrug:
Needs metabolism to produce active drug
[ Prodrug > Inactive Drug ]
- Normal
CYP Phenotype & Genotype:INTERMEDIATE
Active Drug:
Inactivated by metabolism
[ Drug > Inactive Drug ]
- Normal
Prodrug:
Needs metabolism to produce active drug
[ Prodrug > Inactive Drug ]
- Normal
CYP Phenotype & Genotype:POOR
Active Drug:
Inactivated by metabolism
[ Drug > Inactive Drug ]
- Increased efficacy
- Active metabolite may accumulate
- Usually requires lower dose to avoid toxic accumulation
Prodrug:
Needs metabolism to produce active drug
[ Prodrug > Inactive Drug ]
- Decreased efficacy
- 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
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
Treatment benefits can also take weeks to achieve, prolonging the trial and error process even further.
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.
CYP2D6, CYP2C19, CYPA4 and CYP2C9
CYP2D6, CYP2C19, CYPA4 and CYP2C9 are part of the Cytochrome P450 family, and are responsible for metabolizing NAD’s. However, genetic variations of these CYPs result in a spectrum of patient outcomes, ranging from non-response to severe toxicity, even when prescribed an appropriate dose. Additionally, variations in ANKK1 and OPRM1 genes can also contribute to differences in patient responses and drug metabolism.
Neuroactive Drugs with Pharmacogenetic Information
| Amitriptyline | Aripiprazole | Atomoxetine |
| Buprenorphine | Bupropion | Chlordiazepoxide |
| Chlorpromazine | Citalopram | Clonazepam |
| Clonidine | Clomipramine | Clozapine |
| Desipramine | Diazepam | Donepezil |
| Doxepin | Escitalopram | Fluoxetine |
| Fluvoxamine | Gabapentin | Iloperidone |
| Imipramine | Loxapine | Maprotiline |
| Memantine | Mirtazapine | Modafinil |
| Naltrexone | Nefazodone | Nortriptyline |
| Olanzapine | Paroxetine | Perphenazine |
| Phenobarbital | Phenytoin | Pimozide |
| Protriptyline | Risperidone | Sertraline |
| Thioridazine | Trimipramine | Valproic Acid |
| Venlafaxine |
- LIST IS NOT EXHAUSTIVE
Benefits of our Pharmacogenomic Testing
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 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.1
Testing information can be used as an adjunct to other tools for clearer guidance in selecting among various therapeutic choices each patient.
Test Menu
Mental Health P450 Enzyme
- COMT
- OPRM1
- CYP2C19
- ANKK1
- CYP2D6
- CYO3A4
- CYP2C9
Characterizing Metabolic Types
- Extensive Metabolizers (EM)
- Poor Metabolizers (PM)
- Intermediate Metabolizers (IM)
- Ultra-rapid Metabolizers (UM)
References
- Cytochrome P450 Enzyme Genotyping: Optimizing Patient Care Through Pharmacogenetics. Communiqué Mayo Reference Services. 2005. Sep. Vol 30, No. 9
