Hara T, Nishikawa S, Miyazaki H, Ohguro Y
Jpn J Antibiot. 1983 Jan;36(1):150-73.
Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara by Nara et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Toxicological studies of MCR in dogs were carried out by intravenous injection for safety evaluation. 1. Study on subacute toxicity: Beagle dogs were injected intravenously with MCR at the dose levels of 4, 10, 25, 63 mg/kg and 100 mg/kg for 30 days. 2. Study on chronic toxicity: Beagle dogs were injected intravenously with MCR at the dose levels of 1.6, 4 mg/kg and 10 mg/kg for 180 days. The results of the studies are as follows: 1. In the subacute toxicity study, animals died at the dose level of 100g/kg (3 out of 6 animals). Main changes observed were renal disorders and ataxia which showed a close similarity to those seen during intramuscular toxicity studies in dogs. The renal histological disorders occurred at the dose levels of 10 mg/kg and over, but they were slight at the dose levels of 10 mg/kg and 25 mg/kg. Ataxia was observed at the dose levels of 63 mg/kg and over, but its grade was slight at the dose level of 63 mg/kg. 2. In the chronic toxicity study, animals did not die at any dose. Renal disorders occurred; they were almost similar to those observed in the subacute toxicity study and were slight at the dose level of 10 mg/kg. Ataxia was not observed at any dose. 3. The maximum safety dose was equal to in the subacute toxicity and chronic toxicity study (4 mg/kg). Therefore, cumulative toxicity by intravenous injection seemed very slight.
小诺米星（MCR）是由相模小单孢菌非还原变种产生的一种新型氨基糖苷类抗生素，该菌株是奈良等人从相模原采集的土壤中分离得到的。纯化后的抗生素在物理和化学性质上与庆大霉素C复合物极为相似。MCR的抗菌活性具有广谱性，几乎与庆大霉素C复合物相当。MCR对假单胞菌属、变形杆菌属、肺炎克雷伯菌、沙雷菌属等表现出特别高的活性，对一些耐庆大霉素C1a的铜绿假单胞菌菌株也具有高活性。通过静脉注射对MCR进行犬类毒理学研究以进行安全性评估。1. 亚急性毒性研究：将比格犬分别以4、10、25、63mg/kg和100mg/kg的剂量静脉注射MCR，持续30天。2. 慢性毒性研究：将比格犬分别以1.6、4mg/kg和10mg/kg的剂量静脉注射MCR，持续180天。研究结果如下：1. 在亚急性毒性研究中，100mg/kg剂量组的动物死亡（6只动物中有3只）。观察到的主要变化是肾脏疾病和共济失调，这与犬类肌肉注射毒性研究中观察到的情况极为相似。肾脏组织学病变出现在10mg/kg及以上剂量组，但在10mg/kg和25mg/kg剂量组中较轻。共济失调出现在63mg/kg及以上剂量组，但在63mg/kg剂量组中程度较轻。2. 在慢性毒性研究中，任何剂量组的动物均未死亡。出现了肾脏疾病；它们与亚急性毒性研究中观察到的情况几乎相似，在10mg/kg剂量组中较轻。任何剂量组均未观察到共济失调。3. 亚急性毒性和慢性毒性研究中的最大安全剂量均为4mg/kg。因此，静脉注射的累积毒性似乎非常轻微。
