Human 14C-AME Studies

Human AME studies provide definitive information about the nature and amounts of drug metabolites formed in the human body. This allows the comparison of metabolite patters between man and the animal species used for toxicology.

WuXi AppTec DMPK works with established clinical centers in both the USA and China, or a designated clinical trial unit of the sponsor’s choice to evaluate a radiolabeled drug in humans.

Objectives

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

Endpoints

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

The applicability of 14C-AME studies in human

  • To guide the design of clinical drug-drug interaction study according to the major mechanism of drug clearance (metabolic enzymes) in human
  • To determine whether there is a high proportion of metabolites in the human body according to whether any single metabolite in circulation is formed at greater than 10% of total plasma exposure
  • If the existence of high proportion metabolites is confirmed, whether a non-clinical safety assessment is required
  • 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