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Pharmacogenetics for better targeted medication

February 10, 2022

Michel Cameron, PhD
Michel Cameron, PhD
Associate Director ,Pharmacogenomics Medical Science Liaison
LinkedIn

In 2005, a young Toronto mother being treated with codeine following an episiotomy fatally poisoned her 11-day-old baby while breastfeeding. The investigation concluded that the woman had an ultra-fast metabolism, which means her body converted more codeine into morphine. She then unknowingly passed this potent painkiller to her child through her breast milk.[1]

The consequences of a slow or fast metabolism

Michel Cameron, Assistant Director of Pharmacogenetics at Biron, explains that “when a pill is swallowed, it dissolves in the body to produce its effect. It is then metabolized, i.e. transformed by our enzymes (mainly located in the liver) to assist in activating and eliminating it, as the case may be.” However, in some people, these enzymes can be defective.

For the enzyme that metabolizes codeine, CYP2D6, approximately 3% of individuals in Canada are ultra-fast metabolizers and approximately 6% are slow metabolizers.

Drug type Metabolism type Effect
Codeine Slow The level of codeine in the blood is high while the level of morphine remains low = little or no desired effect (the drug may be inactive)
Codeine Fast Codeine levels drop rapidly while morphine levels rise sharply = morphine-induced toxicity (risk of apnea, coma, or even cardiorespiratory arrest)

These figures also vary depending on ethnic origin. For example, fast metabolizers account for about 8% of the North African population. Taking a drug can therefore have radically different consequences depending on the case.[2]

Explaining this phenomenon with genetics

Following the death of the infant in Toronto, studies were conducted. One team followed mothers being treated with Tylenol 3 (containing codeine) whose babies had become ill. Genetic testing revealed that many mothers had ultra-fast metabolisms.[3]

Benefits of pharmacogenetics in choosing a treatment

Not every person reacts the same way to a drug. The same dose may work well for one person and not so well for another, and may even cause serious side effects. This highly specific reaction to treatments is closely linked with our DNA.

Pharmacogenetics, a word that combines pharmacology (the study of drugs) and genetics, studies the influence of our genes on our response to medications. The aim is to improve the efficacy of treatments and the safety of patients.[4]

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How does a pharmacogenetic test work?

The test involves taking a simple saliva sample (which requires no special preparation) and observing the enzymes responsible for metabolism.

A drug is a molecule that the body perceives as a foreign substance, a threat to be eliminated. About thirty types of enzymes are responsible for this mission of metabolization, and each one has its preferences based on the molecules to process. As a result, the mobilized enzymes vary depending on the drug. Our metabolism may then react slowly to certain classes of drugs and quickly to others.

“Pharmacogenetics can often reduce the period of trial and error and help reduce the delay in finding the right medication at the right dose. By testing a list of specific markers, we can then determine the rate of metabolism in individuals.”

Michel Cameron, PhD
Michel Cameron, PhD
Associate Director ,Pharmacogenomics Medical Science Liaison
LinkedIn

Observations made in this way can help in choosing a more efficient treatment and minimize the risk of complications or, on the contrary, of the drug being ineffective.

Various avenues to explore through pharmacogenetics

Although this science, which belongs to the field of personalized medicine, is still relatively new, it is nevertheless of great interest to practitioners.

Pharmacogenetic studies are now underway across Canada on a variety of health problems potentially related to the use of medications. These studies cover topics such as the effect of medications on children with mental health problems. Unfortunately, up to 50% of these children are receiving treatments that are ineffective or cause harmful side effects. Dr. Chad Bousman, a professor of medical genetics at the University of Calgary who is leading the “PGx-SParK” project at his Psychiatric Pharmacogenomics (PsychPGx) Lab, believes a major part of the trial-and-error process could be avoided through pharmacogenetic testing.

In Europe, the possibility of integrating pharmacogenetics into public health systems is currently being explored. The “Ubiquitous Pharmacogenomics” project has been launched to assess the impact of pharmacogenetics on the efficacy, safety and cost of treatments. This landmark research project will provide numerous recommendations on the best way to include pharmacogenetics in the European health-care system. In particular, it will investigate the most effective way to integrate it into medical decision-making without disrupting routine clinical care.

If the project proves successful, the path it lays out will help health-care systems around the world follow this example.

Finally, it should be noted that after a few cases of acute respiratory problems, Health Canada has, since 2013, advised against administering codeine to children under 12 years of age, as some children metabolize it too quickly.[5]

For professional support, we’re here for you.

We provide services that can help your doctor identify the risks of a drug causing adverse side effects or being ineffective.

Book an appointment online or call Biron Health Group’s customer service at 1-855-943-6379.

Sources5
  1. P. Gravel. “À chaque métabolisme sa médication,” November 2008, https://www.ledevoir.com/societe/sante/214915/a-chaque-metabolisme-sa-medication.
  2. Milosavljevic et al. “Association of CYP2C19 and CYP2D6 Poor and Intermediate Metabolizer Status With Antidepressant and Antipsychotic Exposure: A Systematic Review and Meta-analysis,” March 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702196/.
  3. Kelly et al. “More Codeine Fatalities after Tonsillectomy in North American Children,” April 2012, https://pubmed.ncbi.nlm.nih.gov/22492761/.
  4. M. Lhermitte, D. Allorge, F. Broly. “Le polymorphisme génétique des enzymes du métabolisme des médicaments. Une opportunité pour un traitement individualisé,” January 2006, https://www.academie-medecine.fr/le-polymorphisme-genetique-des-enzymes-du-metabolisme-des-medicaments-une-opportunite-pour-un-traitement-individualise/.
  5. Health Canada. “Summary Safety Review - Codeine-containing products - Further Assessing the Risk of Serious Breathing Problems in Children and Adolescents,” July 2016, https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-codeine-prescription-products-cough-further-assessing-risk-serious.html.
Michel Cameron, PhD
Michel Cameron, PhD
Associate Director ,Pharmacogenomics Medical Science Liaison
LinkedIn
Seeking to make the science of genetics accessible for everyone, in 2014 Michel Cameron co-founded BiogeniQ, a company specialized in genetics, where he directed the design and development of pharmacogenomics tests. Today this company is owned by Biron. Michel Cameron holds a Ph.D. in pharmacology from the Université de Montréal and completed postdoctoral studies in pharmacogenomics at the Montreal Heart Institute’s Pharmacogenomics Centre.