Metabolism cage for carbon dioxide trapping studies

Area of Science:

• Pharmacology
• Biochemistry
• Animal Science

Background:

• Pharmacokinetic studies require accurate measurement of drug excretion.
• Metabolism to carbon dioxide (CO2) is a critical excretion pathway that is often overlooked.
• Existing metabolism cages may not efficiently separate all excretion products.

Purpose of the Study:

• To design and construct a novel metabolism cage for precise separation of urine, feces, and expired CO2.
• To validate the cage's separation capabilities in a preclinical study.
• To assess the excretion profile of an orally administered compound, considering CO2 metabolism.

Main Methods:

• A custom-designed metabolism cage was built to segregate urine, feces, and exhaled gases.
• Radioactivity was quantified in urine, feces, and exhaust gases over 14 days post-administration.
• A single oral dose of 26-[14C]cholesterol was administered to assess excretion pathways.

Main Results:

• The metabolism cage successfully separated urine, feces, and expired CO2.
• Less than 1% of administered radioactivity was recovered in urine.
• Significant excretion was observed in feces (61%) and expired CO2 (19%).

Conclusions:

• The developed metabolism cage is effective for simultaneous collection of urine, feces, and expired CO2.
• This tool is suitable for pharmacokinetic studies, particularly for compounds metabolized to CO2.
• Cholesterol undergoes significant metabolism to CO2 in vivo, highlighting the importance of this excretion route.