Low Level Human ADME/Mass Balance Studies

There are circumstances in which the relatively high (100uCi; 3.7MBq) levels of ¹⁴C employed in traditional studies are problematic. Xceleron has employed a microtracer ¹⁴C approach to overcome these limitations under the following circumstances:

- Highly potent compounds where limited amounts of ¹⁴C drug can be administered
- Compounds exhibiting radiochemical instability
- Studies in sensitive populations such as cancer patients, women of child-bearing age and pediatrics
- Long half-life and melanin-binding drugs where levels of ¹⁴C are limited by the dosimetry
- Limiting routes of administration (dermal, ocular, etc.)

Under these circumstances, ¹⁴C must be administered at levels below those detectable by traditional analytical methods such as liquid scintillation counting. Due to the sensitivity of AMS, much lower levels of radioactivity are needed for human regulatory Mass Balance/ADME studies.

Hybrid Human ADME/Mass Balance Studies

There are times when a traditional ¹⁴C study is not adequately supported by liquid scintillation counting. In these circumstances the analytical needs of the study can be completely satisfied through a combination of LSC plus AMS. This arises mostly when levels of ¹⁴C in plasma at later PK timepoints are lower than LSC detection levels.

The majority of drugs using Xceleron AMS data for regulatory filing have used our low level ADME/Mass Balance approach.

Please see the links below for publications:

• Recent applications of AMS in metabolism and PK (2008)
• Regulatory Mass Balance Study for an autoradiolytic oncologic in patients (2007)
• The use of AMS to obtain early human ADME/PK data (2005)
• Human Mass Balance and PK with AMS (2003)