Understanding The Intrinsic And Extrinsic Factors That Alter Drug Exposure And Toxicity

Drugs play a critical role in the prevention and treatment of diseases. Though they are necessary to sustain and enhance the quality of patients’ lives, the increasing number of available drugs on the market leads to a greater potential for drug-drug interactions (DDIs). More complex drug regimens with multiple compounds administered to treat one condition, or different compounds given to treat comorbidities, are contributing factors. DDIs as well as drug-alcohol or food effects are examples of how extrinsic factors can alter the exposure of drugs and cause serious adverse effects or a reduction in efficacy. Furthermore, intrinsic factors such as age, gender, comorbidities or genetics can also potentially alter drug exposure.

Clinical studies can be used to determine the effects these intrinsic and extrinsic factors can have on systemic exposure, and investigate possible interactions. In vitro studies can be conducted to determine whether a drug is a substrate, inhibitor, or inducer of certain metabolizing enzymes and/or intracellular transporters. These are followed by in vivo drug interaction studies to validate whether the nature of these interactions are clinically relevant. Furthermore, orally administered drugs are often studied to explore food interactions (typically with a high fat meal). Depending on the indication, the effects of age, gender, or other intrinsic factors may also need to be examined. Drug and food interaction studies are an integral part of any new drug application and need to be summarized on the drug label.