You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: ["Chemical"].

Please return the output as a JSON object of the format: {"Chemical": ["Arsenic", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].

Only output the JSON object and do not include any additional text.

Abstract:

A perspective on the contribution of metabolites to drug-drug interaction potential: the need to consider both circulating levels and inhibition potency. The 2012 drug-drug interaction (DDI) guidance from the European Medicines Agency (EMA) and the draft DDI guidance from the Food and Drug Administration (FDA) have proposed that metabolites present at >25% of the parent area under the time-concentration curve (AUC) (EMA and FDA) and >10% of the total drug-related exposure (EMA) should be investigated in vitro for their DDI potential. This commentary attempts to rationalize the clinically relevant levels of metabolite(s) that contribute to DDI by considering not only the abundance but also inhibition potency, physicochemical properties, and structural alerts of the metabolite. A decision tree is proposed for levels of metabolites that could trigger in vitro DDI assessment. When the parent is an inhibitor of cytochrome P450s (P450s), clinical DDI studies will assess the in vivo DDI effect of the combination of parent and metabolite(s). When the parent is not a P450 inhibitor, it is important to assess the inhibition potential of abundant metabolites in vitro. The proposal is to apply a default cutoff value of metabolite level which is 100% of the parent AUC. It is important to note that exceptions can occur, and different metabolite levels may be considered depending on the physiochemical properties of metabolites (e.g., increased lipophilicity) and whether the metabolite contains structural alerts for DDI (e.g., mechanism-based inhibition). A key objective of this commentary is to stimulate discussions among the scientific community on this important topic, so that appropriate in vitro metabolism studies are conducted on metabolites, to ensure the safety of drugs in development balanced with the desire to avoid creating unnecessary studies that will add little to no value in ensuring patient safety.
{"Chemical": []}