Radiolabeled absorption, distribution, metabolism, and excretion studies in drug development: why, when, and how?

Chem Res Toxicol. 2012 Mar 19;25(3):513-31. doi: 10.1021/tx300050f. Epub 2012 Feb 21.


Absorption, distribution, metabolism, and excretion (ADME) studies are an integral part of the comprehensive safety evaluation of a new molecular entity, and they represent a standard suite of studies included in the registration package for all new small molecule drugs. In vivo studies in preclinical toxicology species and humans using radiolabeled ((3)H or (14)C) compound provide quantitative assessments of overall routes of excretion of drug-related material, pharmacokinetics of total drug-derived radioactivity in circulation, relative to parent compound and quantitation, and characterization of metabolites in excreta and circulation. These data serve as the starting point for metabolite in safety testing (MIST). These studies involve the administration of a radiolabeled drug to laboratory animals and humans followed by a quantitative collection of excreta and blood. Using appropriate plasma-pooling strategies, these studies could allow for modeling the metabolite exposure at the steady state. Information from the radiolabeled human study is used to design clinical drug-drug interaction (DDI) studies and to obtain a waiver for bioequivalence studies. This article describes the various aspects of conducting ADME studies and the use of radiolabeled analogues of drug candidates to investigate their metabolism and how to compare the exposures of metabolites in humans and toxicology species.

Publication types

  • Review

MeSH terms

  • Absorption
  • Animals
  • Drug Discovery*
  • Humans
  • Pharmaceutical Preparations / metabolism
  • Pharmacokinetics*
  • Radioisotopes / pharmacokinetics*


  • Pharmaceutical Preparations
  • Radioisotopes