Big physics, small doses: the use of AMS and PET in human microdosing of development drugs

Nat Rev Drug Discov. 2003 Mar;2(3):233-40. doi: 10.1038/nrd1037.


The process of early clinical drug development has changed little over the past 20 years despite an up to 40% failure rate associated with inappropriate drug metabolism and pharmacokinetics of candidate molecules. A new method of obtaining human metabolism data known as microdosing has been developed which will permit smarter candidate selection by taking investigational drugs into humans earlier. Microdosing depends on the availability of two ultrasensitive 'big-physics' techniques: positron emission tomography (PET) can provide pharmacodynamic information, whereas accelerator mass spectrometry (AMS) provides pharmacokinetic information. Microdosing allows safer human studies as well as reducing the use of animals in preclinical toxicology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Design
  • Drug Evaluation, Preclinical
  • Humans
  • Mass Spectrometry*
  • Particle Accelerators
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics
  • Tomography, Emission-Computed*


  • Pharmaceutical Preparations