Radiolabeled Non-Clinical In Vivo ADME Study

Generally, radiolabeled preclinical in vivo ADME studies are recommended to be completed in the IND phase or clinical phase I. In general, the sample collection time for mass balance of small animals is 168 h, while the sample collection time for bile excretion is 72 h. This time design can meet the recovery rate of more than 90% in most cases. For large animal mass balance experiments, we recommend sample testing immediately after collection to determine whether the collection time needs to be extended to ensure that the cumulative recovery rate of mass balance reaches 90%, and the total recovery rate in urine and feces for two consecutive days is less than 1%. Radioactive PK time points are generally designed to cover 3 to 5-time half-life of total compound–related materials. Quantitative tissue distribution studies are an essential component of ADME analysis. QWBA or tissue dissection methods can be chosen to deliver the information to understand the relationship between the distribution and accumulation of compounds and/or its metabolites, to support tissue-specific activity, and/or tissue-potential toxicity. Radiolabeled metabolite profiling and metabolite identification studies cover plasma and excreta such as bile, urine, feces, etc., to elucidate the main compound forms and relative exposures present in plasma and excreta, in combination with radioactive detectors and high-resolution mass spectrometry.