Discovering the Invisible Patient with Pharmacogenetic Testing

We are discovering more and more the important role genes play in how our bodies process drugs. Pharmacogenetic testing provides a way to look at a patients’ genes that play a role in drug metabolizing. Identifying unique characteristics of these genes can assist in individualizing pharmacotherapy for chronic pain treatment.¹

Clinicians understand that visible differences between patients, such as age and weight, can affect how that patient will respond to pain treatment. What is currently less understood are the important invisible differences that also affect therapy. A primary cause of variation in drug response is interindividual variations in the genes that encode for the “proteins and enzymes involved in the transport and metabolism of drugs”.² As Meijerman explains, “interindividual differences in the pharmacokinetics (PK) of drugs represent a major clinical problem. Because of these differences, plasma levels of drugs are poorly predictable, which might lead to unexpected toxicities or undertreatment of patients”.² By identifying these genetic variations through a one-time genetic test, we can better prescribe a pharmacotherapy regimen that is optimal for each individual patient.

Specifically, “it is the role of the highly polymorphic CYP2D6 gene that is of the greatest clinical interest with respect to the observed interindividual variability in the opioid response”.¹ The CYP2D6 gene metabolizes many drug classes, including the opioids. Variation in the DNA encoding for these enzymes can cause them to metabolize faster or slower.¹ As also illustrated in the UDM handbook:

DNA sequence variations are associated with:

• Lack of enzymatic activity (poor metabolizer)
• Reduced enzymatic activity (intermediate metabolizer)
• Enhanced enzymatic activity (ultra-rapid metabolizer)

“The use of CYP2D6 genotyping to make therapeutic recommendations to improve therapeutic efficacy and to prevent toxicity in patients is promising and clinically relevant”.² Pharmacogenetic testing can provide us with “invisible” genetic information on a patient’s propensity for a drug reaction that allows us to further objectify each individual’s pain regimen, and thus minimize the practice of trial-and-error prescribing.¹

1. Urine Drug Monitoring: Opioids Handbook
2. Meijerman Irma, Sanderson Linda M., Smits Paul, Beijnen Jos H., Jan H.M. Schellens. “Pharmacogenetic Screening of the Gene deletion and Duplication of CYP2D6.” Drug Metabolism Reviews, 39: 45–60, 2007.