Abstract

Human absorption, distribution, metabolism and excretion (hADME) studies represent one of the most important clinical studies in terms of obtaining a comprehensive and quantitative overview of the total disposition of a drug. This article will provide background on the origins of hADME studies as well as provide an overview of technological innovations that have impacted how hADME studies are carried out and analyzed. An overview of the current state-of-the-art for hADME studies will be provided, impacts of advances in technology and instrumentation on timing of and approaches to hADME studies will be discussed, and a summary of the parameters and information obtained from these studies will be offered. Additionally, aspects of the ongoing debate over the importance of animal ADME studies versus a "human-first, human-only strategy" will be presented. Along with the information above, this manuscript will highlight how over 50 years Drug Metabolism and Disposition has served as an important outlet for the reporting of hADME studies.

Significance Statement Human absorption, distribution, metabolism and excretion studies have and will continue to be important to the understanding and development of drugs. This manuscript provides a historical perspective on the origins of hADME studies as well as advancements resulting in the current-state-of the art practice for these studies.