In addition to genetic variability, several other internal and external factors play a role in medication metabolism. For instance younger patient age is associated with increased metabolism, whereas older age and liver impairment are factors that may decrease metabolism. Race and gender are also known to effect metabolism, as well as exposure to sunlight, alcohol, diet, and polypharmacy.
In the future, pharmacogenetic testing may help clinicians identify patients with chronic pain who may be more or less likely to respond to certain opioids, those who are at higher risk for opioid-related adverse effects, those who require higher than typical opioid doses, and those who are at higher risk for opioid-related drug interactions.
For example researchers know that codeine must be metabolized into morphine in order to have a treatment effect. “Cytochrome P450 allele CYP2D6 is the metabolizing enzyme in the liver; however, 7% of Caucasians are missing one copy of the cytochrome P450 CYPD2D gene,” said Dr. Gupta. “Codeine does not work effectively in these individuals.”
Genetic polymorphisms are also known to play a role in the clearance, serum concentrations, duration of action, and overall efficacy or toxicity of benzodiazepines.