The use of accelerator mass spectrometry to obtain early human ADME/PK data.
There is an increasing recognition within the pharmaceutical industry of the importance of the ADME studies in drug registration. Consequently, there has been a drive in recent times to conduct the ADME studies as early as possible in the development programme. There are, however, regulatory barriers, particularly in the administration of radiotracers to human volunteers, which place limitations on the timing of the ADME studies. Accelerator mass spectrometry (AMS), a technology new to the pharmaceutical industry, is an ultrasensitive technique for measuring tracers such as (14)C. Using AMS, it is possible to lower the radioactive dose administered to humans to a point where many regulatory authorities consider it insignificant. With the removal of the regulatory hurdles, ADME data can be obtained much earlier in the development process. Tracers such as (14)C can be administered in minute amounts in the first in man studies (Phase I), or even in a preregulatory study known as microdosing (or human Phase 0). AMS also enables other studies such as absolute bioavailability to be conducted earlier if required.
Lappin
Graham
G
Xceleron Ltd, York Biocentre, Innovation Way, Heslington, York YO10 5NY, UK.
Garner
R Colin
RC
D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D013678:Technology, Pharmaceutical / Q000379:methods*
D004364:Pharmaceutical Preparations