Metabolite Profiling and Identification

Platform Introduction

Drug metabolism studies run through the entire process of drug development. The information about metabolic pathways and metabolite structures of test compounds is vital for the design and optimization of lead compounds, selecting clinical drug candidates and supporting clinical studies, drug-drug interaction evaluation, and metabolites in safety testing in drug development. Metabolite profiling and identification (MetID) studies are helpful to understand clearance pathways to find potentially active or reactive metabolites and observe disproportionate or unique metabolites. Consequently, it leads to a better understanding of the effects of biotransformation on drug efficacy and safety.

In the process of screening lead compounds, metabolite identification can screen the formation of reactive metabolites and other potentially problematic metabolites. Based on results from in vitro metabolite identification, metabolic soft spots can be quickly identified for optimizing the structure of lead compounds and thus obtain better efficacy.

In the preclinical study stage, in vitro MetID studies of multiple species can be used to obtain cross-species metabolic differences. Comparing the in vivo and in vivo metabolism data of animal can determine if there is a good in vitro-in vivo correlation of metabolism, which can further ensure the reliability of using in vitro metabolism to predict in vivo metabolism in human.

In the phase I clinical trial results from metabolite profiling in human plasma, urine, and feces can reveal qualitative and semi-quantitative exposure of drug-related components to human and drug clearance and metabolic pathways in human. It can be determined if the selection of toxicological species is appropriate after comparing the exposure of metabolites to human and tox species when repeated doses are assessed.

Radio-profiling can effectively study the metabolism, distribution, and clearance of a drug in an animal or human. Profiling and identification of Radiolabeled metabolites in plasma can determine qualitatively and semi-quantitatively drug-related components in the circulating system. The results can establish the basis for deciding the dose-exposure relationship of drugs and may help interpretation if toxicity observed is associated with the parent drug or its major metabolites in plasma. Profiles of Radiolabeled metabolites in bile, urine, and feces can provide information on the drug clearance and metabolic pathways in vivo, which can further help the experimental design of metabolizing enzyme phenotyping and transporter substrate analysis.