Pharmacogenomics and Drug Metabolism

Until pharmacogenomic (PGx) testing was developed, prescribing physicians had to rely on recommended dosing when prescribing a drug therapy for their patients. After taking into consideration a patient’s size, age, co-existing conditions and medications, a provider has FDA approved information on which to determine the appropriate dose of a medication based on response of the majority of test subjects, however, this is not predictive of all patients.

Because of genetic differences among patients, results can vary greatly from being ineffective to causing injury. As a result, patients may be reluctant to follow advice if they have had an adverse reaction to a prescribed medication. An AARP survey of respondents aged 45 years and older resulted in 11% citing “Side Effects” as the reason they did not fill a prescription. PGx testing can improve outcomes by increasing patient compliance and lessening occurrence of ADEs.

Phenotype Definition

Testing for genetic variants can help determine the safest medications and doses by identifying a patient’s phenotype. The metabolic phenotype is a classification of how a given enzyme will metabolize or break down ingested drugs. More than 75% of individuals have a variant on a specific cytochrome that can affect metabolism of commonly prescribed medications. Testing reveals the following phenotypes: (see chart above)

Role of Ethnicity in Drug Metabolism

Frequently, investigation of a particular gene will show patterns in the likelihood of a genetic variant based on race. For instance, variants of the CYP2D6 gene, responsible for the metabolism of a quarter of all approved medications, can be found in the following ethnicities: (see last chart)