Microdosing

Microdosing (or micro-dosing) is a technique for studying the behaviour of drugs in humans through the administration of doses so low ("sub-therapeutic") they are unlikely to produce whole-body effects, but high enough to allow the cellular response to be studied. This allows the observation of a drug's pharmacokinetics with a low risk of side effects. This is called a "Phase 0 study" and is usually conducted before clinical Phase I to predict whether a drug is viable for the next phase of testing. Human Microdosing aims to reduce the resources spent on non-viable drugs and the amount of testing done on animals.

Less commonly, the term "microdosing" is also sometimes used to refer to precise dispensing of small amounts of a drug substance (e.g., a powder API) for a drug product (e.g., a capsule), and when the drug substance also happens to be liquid this can potentially overlap what is termed microdispensing.

The basic approach is to label a candidate drug using the radioisotope 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. The amount of radioactivity administered is typically around 200 nano Curies, which is low as to be considered 'non-radioactive' by authorities.

As only microdose levels of the drug are used, analytical methods are limited. Extreme sensitivity is needed. Accelerator Mass Spectrometry is the most common method for microdose analysis. AMS was developed 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 at Lawrence Livermore National Laboratory. AMS service is now more accessible for biochemical quantitation from several private companies 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 spectrometry methods, measures ionic species according to mass to charge ratio.

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