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Disposition of 2-mercaptobenzimidazole in rats dosed orally or intravenously
Abstract:
The disposition of [14C]-labeled 2-mercaptobenzimidazole (MBI) in male Fischer-344 rats dosed orally (49 or 0.5 mg/kg) or intravenously (0.5 mg/kg) was determined. Absorption of the oral dose was evident, since, in 72 h, most of the radioactivity administered by either route appeared in the urine. Smaller amounts appeared in the feces. In 4 h, 12% of the radioactivity from an intravenous dose of 0.5 mg/kg was excreted in the bile of rats with biliary cannulas. For rats dosed intravenously, the half-life for disappearance of unchanged MBI from plasma was 125 min. In contrast, the terminal half-life for loss of radioactivity from blood was 83 h. The concentration of total radioactivity was higher in liver and kidney tissue than in blood. One of the major urinary metabolites was identified as benzimidazole, and a minor component was tentatively identified as unchanged MBI. Neither of these could be detected in bile.
Insights
The study tracked [14C]-labeled 2-mercaptobenzimidazole (MBI) in rats. MBI was absorbed orally and excreted mainly in urine, with some in feces and bile, indicating rapid systemic elimination.
Area of Science:
- Pharmacokinetics
- Toxicology
- Drug Metabolism
Background:
- 2-mercaptobenzimidazole (MBI) is a chemical compound with potential industrial applications.
- Understanding its metabolic fate and excretion is crucial for safety assessments.
Purpose of the Study:
- To investigate the absorption, distribution, metabolism, and excretion (ADME) of 2-mercaptobenzimidazole (MBI) in male Fischer-344 rats.
- To determine the pharmacokinetic profile of MBI following oral and intravenous administration.
Main Methods:
- Male Fischer-344 rats were administered radiolabeled [14C]-MBI orally (49 or 0.5 mg/kg) or intravenously (0.5 mg/kg).
- Radioactivity was measured in urine, feces, bile, plasma, and tissues over 72 hours.
- Plasma elimination half-life and tissue distribution were analyzed.
Main Results:
- Oral MBI administration showed significant absorption, with most radioactivity excreted in urine within 72 hours.
- Biliary excretion accounted for 12% of the intravenous dose in 4 hours.
- The plasma half-life of unchanged MBI was 125 minutes, while total radioactivity elimination from blood was 83 hours.
- Higher radioactivity concentrations were observed in liver and kidney tissues compared to blood.
- Benzimidazole was identified as a major urinary metabolite.
Conclusions:
- MBI is readily absorbed orally and undergoes rapid elimination primarily via urine.
- The compound is distributed to tissues, with significant metabolism occurring.
- Benzimidazole is a key metabolite, while MBI itself is not detected in bile.