Pharmacometabolomics in drug safety and drug-exposome interactions

Background Pharmacometabolomics is a relatively new field that measures an individual’s metabolome in biofluids to detect prognostic and diagnostic biomarkers of drug response and to provide an effective means to predict variation in a subject’s response to drug treatment. Pharmacometabolomics has the potential to help clinicians determine the effectiveness and safety of a drug on an individual basis. Aim of Review To provide information from the current literature in pharmocometabolomics relevant to drug safety including factors besides genetics that can play a role in how a subject responds to a drug treatment. Pharmacometabolomics studies on drug-induced liver toxicity, the use of pharmacometabolomics to detect and predict drug interactions, and future applications of pharmacometabolomics in drug safety are discussed. Key scientific concepts of the review Pharmacometabolomics can play a role in identifying and/or characterizing toxicity at all stages of drug development. These stages include: pharmacokinetics and ADME; initial toxicity; protective mechanisms; adverse events; late injury; and, injury progression or recovery. Pharmacometabolomics also has the ability to detect endogenous metabolites and markers of other exposure factors including alcohol consumption, impact of the gut microbiome, nutrition, other medications (polypharmacy), dietary supplements, and current individual health-to-disease status, all of which could play a role in patient response to a drug. Pharmacometabolomics alone or in combination with pharmacogenomics can be used to develop customized treatment plans for patients (i.e., personalized medicine) that could significantly reduce adverse events that are sometimes associated with the use of pharmaceuticals.