Pharmaco‐metabolomics opportunities in drug development and clinical research

Abstract

Pharmaco‐metabolomics uses metabolic phenotypes for the prediction of inter‐individual variations in drug response and helps in understanding the mechanisms of drug action. The field has made significant progress over the last 14 years with numerous studies providing clinical evidence for personalised medicine. However, discovered pharmaco‐metabolomic biomarkers are not yet translated into clinics due to a lack of large‐scale validation. Integration of targeted and untargeted metabolomics workflows into pharmacokinetic analysis and drug development can advance the field from bench to bedside. Also, Indian pharmaceutical research and its bioanalytical infrastructure are in a position to take on these opportunities by addressing challenges such as appropriate training and regulatory compliance.

Quantitative Analytical and Computational Workflow for Large-Scale Targeted Plasma Metabolomics

“…To address this issue (Figure 3 and Supplementary Figure S1), we repeated the measurement using equimolar concentrations of previously selected metabolites (Supplementary Table S2). To ensure reliable quantification and peak integration, metabolites were selected based on three criteria: (1) it is detected in at least three concentrations classified as "good" or "broad" (Figure S1), (2) showing a linear relationship between concentration and peak area with an R 2 > 0.9 in at least three data points, and (3) not eluting in void volume with RT > 1 min. In total, we selected 100 metabolites using these criteria and measured them at eight concentrations ranging from 0.03 to 100 µM, using the BEH Z-HILIC column.…”

Drugging the efferocytosis process: concepts and opportunities

“…Immune and metabolic profiles of patients with the same pathology often vary widely 205 . Efferocytosis can engage directly with immune and metabolic pathways and provides opportunities to fine-tune immunological behaviour via metabolic interventions 15 .…”

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

“…They could subsequently play as covariates of the popPK model to eventually recommend a personalized and precise dose for clinicians [ 129 ]. As a result, pharmacometabolomics has been recognized as an opportunity to establish metabolic profiles to elucidate PK and PD characteristics toward drug development and precision medicine [ [129] , [130] , [131] , [132] ]. It could help improve the treatment outcomes of patients with concurrent medical problems [ 13 , 14 ] and be applied for managing TB preventive treatment for the high-risk reactivation of TB [ 133 ].…”

“…It is potential and valuable to explore metabolites predicting alterations in PK parameters and PD responses via the pharmacometabolomics approach [ 122 , [129] , [130] , [131] , [132] ]. This association could be established and should be subsequently validated when more data are available throughout routine care of TB patients ( Fig.…”