Microdosing is a technique for studying the behaviour of compounds in vivo through the administration of doses so low they are unlikely to produce whole-body effects, but high enough to allow the cellular response to be studied. This allows us to see the Pharmacokinetics of the drug with almost no risk of side effects. This is called a Phase 0 study and is usually done before testing on animals to predict whether a drug is viable for the next phase of testing. This is lowering the cost spent on non viable drugs and the amount of testing done on animals as they are what are used in Phase 1 studies.

The basic approach is to label a candidate drug using the isotope carbon-14, and then administer the compound to human volunteers at levels typically about 100 times lower than the proposed therapeutic dosage (from around 1 to 100 micrograms but not above). How the body responds – for example, its conversion of the original drug into other molecules, and how long they stay in the body.

As only microdose levels of the drug are used, analytical methods are limited. Extreme sensitivity is needed. AMS accelerator mass spectrometry is the most common method for microdose analysis. AMS arose in the late 1970s from two distinct research threads with a common goal: an improvement in radiocarbon dating that would make efficient use of datable material and that would extend the routine and maximum reach of radiocarbon dating. AMS is routinely used in geochronology and archaeology, but biological applications began appearing in 1990 mainly due to the work of scientists of Lawrence Livermore National Laboratory AMS service is now more accessible for biochemical quantitation from several private companies Xceleron Ltd. , Corsidus Inc , Vitalea Science and Accium BioSciences and Non-commercial access to AMS is available at the National Institutes of Health (NIH) Research Resource at Lawrence Livermore National Laboratory, or through the development of smaller affordable spectrometers. AMS does not measure the radioactivity of carbon-14 in microdose samples. AMS, like other mass spectroscopy methods, measures ionic species according to mass to charge ratio.

The technique has been developed commercially by the UK-based company Xceleron, set up by the University of York in 1997. In 2005, the company collaborated with several major pharmaceutical companies in the CREAM (Consortium for Resourcing and Evaluating AMS Microdosing) trials, in which microdosing was used to predict the behaviour of five drugs, each with idiosyncrasies that had proved problematic in animal testing. The results pointed to a 70 per cent correspondence between the results obtained using microdosing and those obtained from full-dose studies. In 2006 Xceleron opened in the US and in early 2008, will have identical laboratory capabilities to help more companies improve their drug development programs.

It is reported that 75 per cent of the 20 leading pharmaceutical companies have now used microdosing in drug development, and the use of the technique has been provisionally endorsed by both the European Medicines Agency and the Food and Drug Administration. Furthermore it is expected that by 2010, human microdosing will have gained a secure foothold at the discovery-preclinical interface driven by early measurement of candidate drug behavior in humans and by irrefutable economic arguments.

In January 2006, the European Union Microdose AMS Partnership Programme (EUMAPP) was launched, under which 10 organisations from five different countries (United Kingdom, Sweden, Netherlands, France and Poland)will study and validate various approaches to the basic AMS technique.


  • The use of accelerator mass spectrometry to obtain early human ADME/PK data G Lappin & R C Garner Expert Opinion in Drug Metabolism and Toxicology (2005) 1(1):23-31
  • Improved early clinical development through human microdosing studies I Wilding & J Bell Drug Discovery Today 2005 July 1;10(13):890-4

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