DRUG METABOLISM — PGX COMPREHENSIVE

Overview:

DRUG METABOLISM — PGX COMPREHENSIVE

Drug metabolism rates vary among patients. Some patients metabolize a drug so rapidly that therapeutically effective blood and tissue concentrations are not reached; in others, metabolism may be so slow that usual doses have toxic effects.

Drug response differences are associated with differences present in individuals’ genetic makeup. Typically, people have two copies of each gene. Those with extra gene copies produce too much of the CYP2D6 enzyme and process the drug very fast. As a result, their bodies convert the painkiller drugs like codeine to their active form morphine so quickly that a standard dose of codeine leads to morphine toxicity. In contrast, some variants of CYP2D6 that vary by a single difference in their DNA sequence create an enzyme that doesn’t work. People with these variants process codeine slowly, if at all, leading to little, if any, pain relief.

Examples of genetic markers included in the PGx comprehensive panel:

The genetic variation in response to drugs is referred to as pharmacogenomics (also known as pharmacogenetics). Pharmacogenetics looks at how individuals’ DNA affects the way they respond to drugs. Knowing the patient’s pharmacogenetics in advance can help mitigate adverse drug reactions among genetically vulnerable individuals and provide information for improved dosage recommendations for therapeutic effect.

Kashi Clinical Lab offers pharmacogenetics testing to providers helping them minimize trial and error approach in prescribing medications to treat pain, depression, anxiety, and other mental health issues. Although drug metabolism rates are influenced by various factors, it is well known that an individual’s genetic makeup may predispose them to adverse effects and reduced efficacy of medications.

Example Table of CYP Metabolizers by Phenotype

Results from Kashi Health’s Pain Management Panel classify patients by how effectively a patient is likely to metabolize a medication. This classification is based on how many copies of functional or variant alleles are inherited. In general, the genetic variability of CYP genes can be grouped into four phenotypes: ultra-rapid metabolizers (UM), normal (extensive) metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM).

TYPE OF METABOLIZER and GENETIC VARIABILITY EFFECTS

• Ultra-rapid metabolizer (UM): Increased enzymatic activity due to duplications or multiplications of the functional allele
• Extensive metabolizer (EM: Normal enzymatic activity due to the presence of at least one functional allele
• Intermediate metabolizer (IM): Moderately decreased enzymatic activity with either two decreased activity alleles or one decreased activity allele and one null allele

Limitations of pharmacogenomics

Interactions with environmental elements and other medications need to be taken into consideration with the genetic makeup of the patient when determining the efficacy of a drug. Rare genetic differences may not be detected because the panel screens for the most common and well-documented gene variants.