There is no doubt that human microdosing holds significant promise as an analytical tool. Evidence to date actually suggests that the practice may be a better predictive tool of human pharmacokinetics than alternative methods. By combining physiologically based modelling techniques with microdosing, this work can lead to much more reliable predictions in the future.
The practice of microdosing has gained momentum in recent years and is defined as using 1 percent of a pharmacologically active dose. The method is believed to have the potential to better obtain personalized medicines for the treatment of a variety of diseases. Since administration of these doses are so low, the drugs are unlikely to produce whole-body effects but have concentrations adequately permitting absorption, distribution, metabolism, and excretion. So in effect, microdose studies are not intended to produce any adverse pharmacologic effects in humans, but may produce useful pharmacokinetic information to assist in further development of the compound.
The potential for decreased Research & Development expenditures has made microdosing an attractive strategy, particularly in the case of resources spent on nonviable drug candidates and animal testing. Microdose studies are conducted in the Phase 0 clinical trial. During this stage, issues pertaining to drug metabolism and pharmacokinetics are addressed. Microdosing, therefore, allows not only for the selection of the drug candidates more likely to be developed successfully, but also for the determination of the first dose for the subsequent Phase I clinical trial.
With these potential benefits, more research is required to guarantee the accuracy and efficiency of microdosing. It is important to remember that there is an assumption of linearity between the microdose and the full dose drug. The human body’s response to a microdose could result in the rejection of a compound that is acceptable based on microdose data but rejected subsequently when used in pharmacological doses. It is also important to consider the rates of absorption, and how they can be affected by compound metabolism and solubility. This is perhaps even more complex for researchers aiming to bring new personalized medicines to the market. As a preventative measure a genetic test is very helpful before drug exposure, and of course enzymes should be implemented in order to control drug transport and metabolism.
Putting it All Together
There is no doubt that human microdosing holds significant promise as an analytical tool. Evidence to date actually suggests that the practice may be a better predictive tool of human pharmacokinetics than alternative methods. By combining physiologically based modelling techniques with microdosing, this work can lead to much more reliable predictions in the future. Ultimately, progress in drug discovery is largely achieved through trial and error. The same ideology can be applied to the practice of microdosing. Future biologics have the potential to be made quicker, easier, and cheaper, also leading to the possibility of more personalized medicines getting to market. However, it will be important to carefully evaluate the benefits and challenges against specific research objectives, budget limitations and desired outcomes.
 [“Human microdosing for the prediction of patient response,” March 2010, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113695/]
 [ “Phase 0 clinical trials: conceptions and misconceptions,” June 2008, http://www.ncbi.nlm.nih.gov/pubmed/18536551/]
 [ “Big physics, small doses: the use of AMS and PET in human microdosing of development drugs.,” March 2003, http://www.ncbi.nlm.nih.gov/pubmed/12612650]