Human absorption, distribution, metabolism and excretion properties of drug molecules: a plethora of approaches

Br J Clin Pharmacol. 2014 Dec;78(6):1185-200. doi: 10.1111/bcp.12468.


Human radiolabel studies are traditionally conducted to provide a definitive understanding of the human absorption, distribution, metabolism and excretion (ADME) properties of a drug. However, advances in technology over the past decade have allowed alternative methods to be employed to obtain both clinical ADME and pharmacokinetic (PK) information. These include microdose and microtracer approaches using accelerator mass spectrometry, and the identification and quantification of metabolites in samples from classical human PK studies using technologies suitable for non-radiolabelled drug molecules, namely liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. These recently developed approaches are described here together with relevant examples primarily from experiences gained in support of drug development projects at GlaxoSmithKline. The advantages of these study designs together with their limitations are described. We also discuss special considerations which should be made for a successful outcome to these new approaches and also to the more traditional human radiolabel study in order to maximize knowledge around the human ADME properties of drug molecules.

Keywords: investigational drugs; metabolism; pharmacokinetics; radioactive tracers.

MeSH terms

  • Carbon Radioisotopes
  • Chromatography, Liquid
  • Humans
  • Magnetic Resonance Spectroscopy
  • Pharmacokinetics*
  • Tandem Mass Spectrometry
  • Tissue Distribution


  • Carbon Radioisotopes