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[Toxicological studies on a new cephamycin, MT-141, IV. Its acute toxicity in beagle dogs]
Abstract:
The acute toxicity of MT-141 was studied in adult Beagle dogs with intravenous (i.v.) or intramuscular (i.m.) administration to obtain following results. MT-141 at the doses ranging from 2,500 to 7,500 mg/kg i.v. caused no effect on life, bodyweight, food intake, eyeground and ECG in male and female Beagle dogs. MT-141 produced an increase in water intake, urine volume, WBC and LAP and a decrease in Lymph., U-Na, U-K and OP, but any histopathological change was not caused in the organs and tissues. It is suggested that these changes in blood, serum and urine are due to mechanical and transient effects induced by infusing a large volume of hypertonic solution of MT-141 into cephalic vein. When 1,000 or 2,000 mg/kg of MT-141 was injected into the muscles of hind legs, the hind legs had difficulty in walking. It is very probable that this change was due to mechanical effects induced by injecting a hypertonic solution of MT-141 at a rate of 70--130 ml/dog. An injection of 1,000 or 2,000 mg/kg i.m. of MT-141 changed activity of GPT, GOT and CPK in the serum within the limit of physiological variations but did not caused any effect on the other toxicological parameters such as bodyweight, food intake, water intake, urine volume, eyeground examination, ECG and histopathological examination. It is concluded from the above-mentioned results that MT-141 at the dose of 2,500--7,500 mg/kg i.v. or 1,000--2,000 mg/kg i.m. has no significant toxicity in Beagle dogs.
Insights
MT-141 showed no significant toxicity in Beagle dogs via intravenous or intramuscular routes. Transient effects observed were likely due to the hypertonic solution
Area of Science:
- Pharmacology and Toxicology
- Preclinical Drug Safety Assessment
Context:
- Evaluating the safety profile of novel compounds is crucial in drug development.
- Beagle dogs are a standard model for preclinical toxicity studies.
Purpose:
- To determine the acute toxicity of MT-141 in adult Beagle dogs.
- To assess the effects of intravenous (i.v.) and intramuscular (i.m.) administration of MT-141.
Summary:
- Intravenous administration of MT-141 (2,500–7,500 mg/kg) did not affect vital parameters, body weight, or cause histopathological changes.
- Minor transient changes in blood and urine parameters were observed with i.v. administration, attributed to the hypertonic nature of the solution.
- Intramuscular injection (1,000–2,000 mg/kg) caused temporary hind leg mobility issues, likely mechanical, with no significant impact on other toxicological parameters.
Impact:
- MT-141 demonstrates a favorable acute toxicity profile in Beagle dogs.
- Findings support the potential for further investigation of MT-141 in preclinical and clinical settings.
- The study provides essential safety data for the development of MT-141.