Microdosing and the Vanishing Zero

The July 2005 issue of Drug Discovery News featured an interesting editorial (p. 8) by Randall Willis on the topic of microdosing in the "nether region between preclinical and clinical testing - Phase 0."  To some who have been alerted to the WSJ article of July 25, 2005 (posted here elsewhere), the regimen involved here may appear to intersect the conditions being used to study the effects on human health of ultra trace agents in the environment, namely parts per billion or smaller.  Microdosing simply involves the administration of sub-pharmacological or sub-therapeutic doses - micrograms - of a drug candidate to humans.  At least one study seems to indicate that microdose data are largely predictive of therapeutic dose response.            

Mainstream chemists interested in the nuances of chemical analysis would appreciate the fact that these protocols are only possible because of the technical advances in instrument detection limits that allow "almost single molecule detection."  Greater complexity comes from a realization that "sub-dosing" involves microgram quantities of chemical agents, similar to many environmental exposure levels (ppb).  Compare that to therapeutic dosages of an agent like perchlorate (historically used in treatment of Graves' disease) that has been administered at dosages of hundreds of milligrams per day, thousands of times higher than environmental exposure levels.  Small wonder that uncertainty drives many an environmental debate.

More on the topic:  www.drugdiscoverynews.com.