Abstract
Background: Microtracing/microdosing is an innovative technology that can revolutionize the current paradigm of clinical drug development. Typically, a very small amount of the drug, i.e., 'microdose', which is less than 100 micrograms (or 30 nmoles for proteins), is administered to humans. Because this is much smaller than 1/100 of the pharmacologically active dose in many cases, microtracing/microdosing technology can be employed at a very early stage of clinical drug development even when there is limited animal toxicology data. Furthermore, in order to trace minute doses, an accelerator mass spectrometer (AMS) is required and the compound should be labeled, typically with 14C. The microtracing/microdosing study allows clinical drug development scientists for generating the intravenous pharmacokinetics, mass balance, metabolite profiling, and absolute bioavailability data much easier, faster, and at a significantly lower cost. The objectives of the present study were 1) to investigate how the AMS-enabled microdosing/microtracing study has been utilized to streamline clinical drug development, and 2) to evaluate the perspectives for the future potential of the AMS-enabled microdosing/microtracing study from industry drug development scientists
Method: We performed a systematic review of published papers reporting the results of AMS-enabled microdosing/microtracing drug development study. In addition, we took a survey of a group of drug development researchers.
Results: The number of the clinical studies that used 14C and AMS dramatically increased from only 3 in 2001-2005 to 59 in 2011-2015. The survey showed that 31.6% of new drug development scientists were planning to perform microtracing/microdosing studies. Furthermore, 73.7% of survey responders replied that they would consider AMS-based microtracing/microdosing studies if there is a well-established service provider.
Conclusion: This study confirmed that the frequency of AMS-based microtracing/microdosing studies for drug development has been in a steady increase for the past decade or so. This increase was partly because several issues of AMS application in the previous era, such as dose-linearity, sample pre-processing, and high cost, have been adequately addressed. In conclusion, AMS-based microtracing/microdosing studies have been steadily employed in clinical drug development, which is expected to increase further in the future.
