Pharmacometabolomics for the Study of Lipid-Lowering Therapies: Opportunities and Challenges

Abstract

Lipid-lowering therapies are widely used to prevent the development of atherosclerotic cardiovascular disease (ASCVD) and related mortality worldwide. “Omics” technologies have been successfully applied in recent decades to investigate the mechanisms of action of these drugs, their pleiotropic effects, and their side effects, aiming to identify novel targets for future personalized medicine with an improvement of the efficacy and safety associated with the treatment. Pharmacometabolomics is a branch of metabolomics that is focused on the study of drug effects on metabolic pathways that are implicated in the variation of response to the treatment considering also the influences from a specific disease, environment, and concomitant pharmacological therapies. In this review, we summarized the most significant metabolomic studies on the effects of lipid-lowering therapies, including the most commonly used statins and fibrates to novel drugs or nutraceutical approaches. The integration of pharmacometabolomics data with the information obtained from the other “omics” approaches could help in the comprehension of the biological mechanisms underlying the use of lipid-lowering drugs in view of defining a precision medicine to improve the efficacy and reduce the side effects associated with the treatment.

Revolutionizing Blood Collection: Innovations, Applications, and the Potential of Microsampling Technologies for Monitoring Metabolites and Lipids

“…Therapeutic drug monitoring (TDM) is a specialized clinical practice that consists of the measurement of the concentration in plasma or blood of a wide range of drug classes, such as antiepileptics, antimicrobial agents and immunosuppressants [ 86 , 87 , 88 , 89 , 90 , 91 ]. Most of the studies are focused on the quantification of the drugs in blood or serum using DBS [ 92 ], but in recent years, pharmacometabolomics has emerged, aiming at the evaluation of the metabolic fingerprints following drug administration [ 93 ]. Even with some limitations, i.e., the standard protocol for sample preparation and storage, environment influence, and ethnicity, this type of study could be useful to evaluate drug toxicity and pharmacokinetics, but also predict the pharmaceutical answer and its pharmacodynamics [ 94 ].…”

Review on analytical technologies and applications in metabolomics

“…The application of metabolomics in pharmacology gives rise to a new field called "pharmacometabolomics" [136][137][138]. The basic tenet of pharmacometabolomics is to determine the metabolism of the drug itself and its influence on the metabolic process of the organism during treatment.…”

Proteomics and Metabolomics in Biomedicine

“…Some of these revolve around the application of proteomics and metabolomics to biomarkers or pathway discovery for the diagnosis and management of cancer [55][56][57], while others evaluate the impact of metabolomics in the recognition of peritoneal membrane dysfunctions in patients undergoing peritoneal dialysis [58]. Opportunities and challenges have been discussed with regards to pharmacometabolomics for the study of lipid-lowering therapies [59] and for the enrichment and characterization of protein lipidation as a form of post-translational modification [60]. Finally, one article extensively describes the proteomic and metabolomic signatures of COVID-19, emphasizing the latest discoveries regarding the disease and the efforts provided by the omics community, unifying them under the term COVIDomics [61].…”