Comparative physiological disposition of two nitrofuran anti-microbial agents

Area of Science:

• Pharmacology
• Drug Metabolism
• Gastroenterology

Background:

• Nitrofuran derivatives like nifurzide and nifuroxazide are used for acute infectious diarrhea.
• Understanding their physiological disposition is crucial for assessing efficacy and safety.

Purpose of the Study:

• To evaluate the physiological disposition of nifurzide and nifuroxazide in humans and animals.
• To determine the absorption, distribution, metabolism, and excretion (ADME) profiles of these antimicrobial agents.

Main Methods:

• Oral administration of a single dose (600 mg) in humans.
• Administration of radiolabeled compounds (14C-nifurzide and 14C-nifuroxazide) to rats (10 mg kg-1).
• Analysis of blood, urine, and feces for unchanged drug and metabolites.
• Whole-body autoradiography in rats to track radioactivity distribution.

Main Results:

• No unchanged nifurzide or nifuroxazide was detected in human blood or urine.
• In rats, 5% (nifurzide) and 17% (nifuroxazide) of the dose were excreted in urine as metabolites over 48 hours.
• Fecal excretion showed 20% unchanged nifuroxazide and 100% unchanged nifurzide.
• Autoradiography revealed most radioactivity remained within the gastrointestinal lumen in rats.

Conclusions:

• Nifurzide and nifuroxazide undergo significant metabolism, with minimal unchanged drug excreted renally in both humans and rats.
• Renal excretion primarily involves metabolites, not the parent compounds.
• The majority of these nitrofuran derivatives remain in the gastrointestinal tract after oral administration, suggesting localized action.