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Absorption, distribution and excretion of neocarzinostatin (NCS) in mice after oral administration
Abstract:
Distribution, excretion and toxicity of an antitumor protein, neocarzinostatin (NCS) were examined in mice after oral administration. The oral LD50 1 g/kg after intravenous injection. After oral administration of 200 mg/kg of NCS, the tissue level was low but detectable in lung, skin and pancreas in addition to the tissues of the gastrointestinal tract. The NCS level in lung and skin remained constant through 6 hours. In gastrointestinal tissues after oral administration the level was higher in the stomach than the large intestine or small intestine. The total recovery of orally administered NCS in feces of mice was 26.5% of the given dose during the first 12 hours. Inactivation of NCS by homogenates of small and large intestines (about 50%) was found in in vitro experiments.
Insights
Oral administration of the antitumor protein neocarzinostatin (NCS) resulted in low but detectable tissue levels in mice, with significant gastrointestinal inactivation and fecal excretion.
Area of Science:
- Pharmacology and Toxicology
- Cancer Research
Background:
- Neocarzinostatin (NCS) is an antitumor protein with potential therapeutic applications.
- Understanding the oral bioavailability, distribution, and excretion of NCS is crucial for its clinical development.
Purpose of the Study:
- To investigate the distribution, excretion, and toxicity of neocarzinostatin (NCS) following oral administration in mice.
- To determine the oral LD50 of NCS and its tissue-specific levels after ingestion.
Main Methods:
- Oral administration of NCS to mice at a dose of 200 mg/kg.
- Measurement of NCS levels in various tissues (gastrointestinal tract, lung, skin, pancreas) over time.
- Quantification of NCS recovery in feces.
- In vitro experiments to assess NCS inactivation by intestinal homogenates.
Main Results:
- Oral LD50 of NCS was determined to be 1 g/kg.
- Detectable levels of NCS were found in the gastrointestinal tract, lung, skin, and pancreas.
- NCS levels in lung and skin remained stable for up to 6 hours post-administration.
- Higher NCS concentrations were observed in the stomach compared to the small and large intestines.
- Approximately 26.5% of the orally administered NCS was recovered in feces within 12 hours.
- In vitro studies showed significant inactivation (around 50%) of NCS by small and large intestinal homogenates.
Conclusions:
- Oral administration of NCS leads to limited systemic distribution but detectable levels in specific organs.
- The gastrointestinal tract plays a significant role in NCS inactivation and excretion.
- Further research is needed to optimize oral delivery strategies for NCS.