Human Radiolabel-AME Studies

Definitive Information for Better In-Human Outcomes

Human Absorption, Metabolism, Excretion (AME) studies provide the definitive information needed to better understand the nature and amounts of drug metabolites formed in the human body – and data reveals the biotransformation, disposition and clearance of the parent compound and its metabolites. This allows comparison of metabolite profiles between humans and the animal species used for toxicology.

WuXi AppTec works with established clinical centers in the U.S. and China, as well as client-designated clinical trials units, to conduct evaluations of radiolabeled drugs in humans.

Objectives 

• To determine the mass balance and routes of elimination of a radiolabeled test compound
• To determine the relative exposure levels of the parent compound and metabolites
• To identify and elucidate structures of key metabolites in circulation and excreta
• To determine the clearance mechanisms

Endpoints

• Quantify the total radioactivity in urine and feces to obtain the drug’s mass balance and determine the major excretion routes
• Identify the major circulating metabolites and determine the clearance mechanism of the major drug-related metabolites
• Determine the total plasma and blood concentration and pharmacokinetic (PK) parameters of total radioactivity (=total drug-related mass)

Applicability of Radiolabel Human-AME Studies

• To guide the design of clinical drug-drug interaction studies in accordance with the major mechanism of drug clearance (metabolic enzymes) in humans
• To determine the major metabolites in the human body and whether any single metabolite in circulation is presented at >10% of total plasma exposure
• If the existence of major circulating metabolites is confirmed, drive follow-up assessments of possible human unique or disproportionate metabolites and possible additional non-clinical safety assessment, in accordance with “Guidelines for Industry Safety Testing of Drug Metabolites” (MIST) of China’s National Medical Products Administration (NMPA) and/or U.S. Food and Drug Administration (FDA) Guidance for Industry, Safety Testing of Drug Metabolites, Pharmacology/Toxicology, Revision 2, March 2020 (MIST Guidance) In accordance with “Guidelines for Industry Safety Testing of Drug Metabolites” of CFDA
• To guide dose level selection in Phase II and Phase III clinical trials for a special population