Mass balance studies investigate the absorption, distribution, metabolism, and excretion (ADME) of a drug following a single administration to humans. The drug is radiolabeled to allow determination of drug disposition and assessment of major metabolic pathways. Radiolabeling can also provide extensive information on exposure to the parent drug and its metabolites, and the rate and route of elimination.

Accium has successfully delivered on a wide range of AMS-based mass balance studies. Each study was customized to address particular challenges that were specific to each program. Here is an outline of the various approaches we have employed in the design and conduct of these studies:

Clinical Design

• Enroll six to eight subjects.

• Determine a pharmacologic single dose of target compound.

• Dose radiolabel compound as low as 100 nCi.

• Collect 1 to 2 mL plasma, whole blood, and all urine and fecal samples for analysis.

Study Phase

• The sensitivity of AMS technology ensures that the terminal phase drug related concentrations in plasma and whole blood are accurately and precisely defined.

• Process fecal samples using optimized blending prior to AMS analysis.

• Measure total carbon concentration in each urine and fecal sample for accurate reporting.

• Provide elimination concentrations and % dose recovered and % cumulative dose recovered in collection period.

Advantages

• Permits recovery of ¹⁴C-total in urine and fecal collections without method development.
• Eliminates dosimetry requirements because of smaller nCi detection range.
• Prevents radiolysis for certain drug products administered at high specific-activity.
• Smaller dose samples can be shipped and processed as non-radioactive.
• Can proceed in tandem with metabolite profiling studies.

References

See resources 1 and 3.