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Disposition of [4-14C]mofebutazone in the rat
Abstract:
The absorption and elimination of radioactivity after the oral or intraperitoneal administration of[4-14C]mofebutazone was studied in rats. The blood concentration of radioactivity reached a maximum after about 0.7 h, fell rapidly until about 2 h, and then declined slowly. There was sometimes a second peak between 3-6 h. Elimination of radioactivity in urine and feces was extensive and rapid. Over a 24 h period, 73% of the orally administered radioactivity was eliminated in the urine and 15% in the faeces; most of this was eliminated during the first 8 h (89% of the urine radioactivity, 56% of the faeces radioactivity). In anaesthetized rats with cannulated bile ducts, 94% of the intraperitoneally injected radioactivity was eliminated in the bile over a 6 h period. Most of the radioactivity (about 85%) eliminated in the bile and the urine was in the form of a glucuronide and only small amounts less than 10%, was in the form of mofebutazone.
Insights
Radioactive mofebutazone was rapidly absorbed and eliminated in rats, primarily via urine and bile. Most eliminated radioactivity was in glucuronide form, indicating extensive metabolism.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Toxicology and Pharmacology
Background:
- Mofebutazone is a non-steroidal anti-inflammatory drug (NSAID).
- Understanding its absorption, distribution, metabolism, and excretion (ADME) is crucial for safety and efficacy.
Purpose of the Study:
- To investigate the pharmacokinetic profile of [4-14C]mofebutazone in rats.
- To determine the routes and extent of radioactivity elimination after oral and intraperitoneal administration.
Main Methods:
- Administration of radiolabeled mofebutazone ([4-14C]mofebutazone) to rats via oral and intraperitoneal routes.
- Measurement of radioactivity in blood over time.
- Quantification of radioactivity excreted in urine, feces, and bile.
Main Results:
- Blood radioactivity peaked around 0.7 hours, with rapid initial decline and occasional secondary peaks.
- Extensive and rapid elimination of radioactivity occurred, with 73% in urine and 15% in feces within 24 hours after oral administration.
- Intraperitoneal administration resulted in 94% elimination via bile within 6 hours.
- The majority of eliminated radioactivity (approx. 85%) was in glucuronide metabolite form, with less than 10% as unchanged mofebutazone.
Conclusions:
- Mofebutazone undergoes rapid absorption and extensive elimination in rats.
- Biliary excretion is a significant route, particularly after intraperitoneal administration.
- The drug is extensively metabolized, primarily to its glucuronide conjugate, before excretion.