Genes and Drugs
Patients differ in response to drugs. This variation can range from potentially life threatening adverse drug reactions to an equally serious lack of therapeutic efficacy even after taking the standard and safe dose of a drug. As knowledge of the human genome increases, the genetic differences between individuals play an important role in this variability. To help predict potential variability, physicians are increasingly relying on pharmacogenomic testing to provide important clinical information about the genetic status of their patients.
Pharmacogenomics examines the influence of genetic differences to help understand the clinically relevant variation in drug response. Pharmacogenomic testing applies DNA technology to identify these naturally occurring differences to assist optimization of pharmacotherapy for individual patients. These advances in personalized medicine get the right drug, to the right patient, at the right dose, at the right time.
CYP2D6, CYP3A4/5, & Opioid Metabolism
The ability of a person to metabolize certain opioids is based on the number and functional status of CYP2D6 and CYP3A4/5 genes. Defective genes may lead to impaired metabolism, while gene duplication leads to enhanced drug metabolism. CYP2D6 is characterized with approximately 10% of the population having a slow acting form of this enzyme (poor metabolizer) and 7% a super-fast acting form (ultra metabolizer), and 35% are carriers of a non-functional 2D6 allele. Elevating the risk of ADRs when these individuals are taking multiple drugs.
Cytochrome P450 (CYP) is a set of proteins that help the body metabolize a wide variety of foreign compounds. Certain genetic variants of CYP450 alter the rate of drug metabolism and may cause increased or decreased drug efficacy or adverse drug reactions. In particular, CYP2D6 and CYP3A4/5 are believed to metabolize -30% of all pharmaceuticals. They are known to be essential for metabolism of many commonly prescribed opioids including: codeine, dihydrocodeine, oxycontin, hydrocodone.
Pharmacogenomic Testing for Opioids
Testing provides several clinical benefits:
• Assist physician to make individualized analgesic choice and dose.
• Mitigate regulatory agency scrutiny by providing additional clinical decision making evidence for several schedule II narcotics.
CYP2D6 genotype is one of multiple pieces of information that clinicians should consider in guiding their therapeutic choice for each patient.
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