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[Toxicological studies on a new cephamycin, MT-141. VII. Its locally-irritating activity in rabbits]
Abstract:
The local irritation of MT-141 was compared with that of cefmetazole (CMZ) in rabbits to obtain following results. Microscopic observations revealed that the irritative activity of 10% solution of MT-141 in blood vessels was not so much different from that of saline and 10% solution of CMZ when they were injected twice a day into vein retroauricularis of rabbits for 7 days. The histopathological changes induced by 10% solution of MT-141 were similar to those by 10% solution of CMZ but somewhat different from those by saline, because both compounds caused slight necrosis in the tissue around vessels. Histopathological observations suggested that the occurrence of necrosis was due to the leakage of them during injections. The local irritation of MT-141 by an injection of 1 ml of its solution into muscle vastus lateralis was compared with that of CMZ in rabbits. The potencies of irritative activity of the test solutions were summarized in the following order; saline less than 5% MT-141 less than 10% MT-141 not equal to 10% CMZ much less than 0.75% acetic acid less than 6.0% acetic acid. The above-mentioned results suggest that MT-141 has low irritating activity when injected through intravenous or intramuscular route for clinical practice as 5% or 10% solution.
Insights
MT-141 exhibits low local irritation potential, comparable to cefmetazole (CMZ), in rabbit studies. Both intravenous and intramuscular injections of MT-141 demonstrated minimal adverse effects, suggesting its suitability for clinical use.
Area of Science:
- Pharmacology
- Toxicology
- Preclinical Research
Context:
- Evaluating the local irritation of novel pharmaceutical compounds is crucial for determining safe administration routes.
- Cefmetazole (CMZ) serves as a benchmark antibiotic for comparison in irritation studies.
- Rabbit models are commonly used for preclinical assessment of drug-induced tissue reactions.
Purpose:
- To compare the local irritative activity of MT-141 with cefmetazole (CMZ) and saline in rabbits.
- To histopathologically assess tissue changes following intravenous and intramuscular administration of MT-141.
- To determine the safety profile of MT-141 for potential clinical application.
Summary:
- Intravenous injections of 10% MT-141 in rabbits showed minimal irritation, similar to saline and 10% CMZ, with slight necrosis possibly due to leakage.
- Intramuscular injections revealed MT-141's irritative activity was lower than acetic acid and comparable to CMZ at equivalent concentrations.
- Histopathological analysis indicated MT-141 possesses low local irritation potential via both intravenous and intramuscular routes at 5% and 10% concentrations.
Impact:
- The findings support the potential clinical use of MT-141, indicating a favorable local tolerance profile.
- This research contributes to the safety assessment of new antibiotics, guiding formulation and administration strategies.
- Understanding the comparative irritation of MT-141 and CMZ aids in selecting appropriate therapeutic options.