Novel strategies for microdose studies using non-radiolabeled compounds

Adv Drug Deliv Rev. 2011 Jun 19;63(7):532-8. doi: 10.1016/j.addr.2011.02.004. Epub 2011 Feb 21.


Microdose studies using non-radiolabeled compounds enable assessment of the clinical pharmacokinetics of drug candidates in humans without the need to synthesize radiolabeled compounds. We have demonstrated that the quantification limits of many drugs measured by LC-MS/MS are low enough to allow estimation of their pharmacokinetic parameters following administration of a microdose. Our previous microdose studies with LC-MS/MS demonstrated the linear pharmacokinetics of fexofenadine between microdoses and therapeutic doses. We also obtained time profiles of plasma concentrations of nicardipine and its multiple metabolites following administration of a microdose. A significant advantage of using non-radiolabeled compounds is the ability to perform cassette microdose studies. By administering multiple drug candidates to the same subject, we can select compounds with appropriate pharmacokinetic properties simultaneously. We can also clarify major factors dominating the pharmacokinetics of drug candidates by cocktail microdosing of the test compounds and probe substrates with or without specific inhibitors for enzymes/transporters.

Publication types

  • Review

MeSH terms

  • Chromatography, Liquid / methods
  • Clinical Trials, Phase I as Topic / methods*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Interactions
  • Humans
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / metabolism
  • Pharmacokinetics
  • Tandem Mass Spectrometry / methods


  • Pharmaceutical Preparations