Abstract
KW-1062 is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis 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 KW-1062 is broad-spectrum and almost equal to that of gentamicin C complex. KW-1062 exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosastrain resistant to gentamicin C1aToxicological studies of KW-1062 were carried out for safety evaluation as follows:
1. Studies were carried out to assess acute toxicity, when administered by intravenous, intramuscular, intraperitoneal, subcutaneous and oral routes to ICR strain mice and Wistar strain rats comparing with gentamicin, and by intramuscular injection to Beagle strain dogs.
2. Studies on subacute toxicity were carried out by intramuscular administration (10, 25, 63, 156, 247mg/kg) to Wistar strain rats for 30 days comparing with gentamicin (25, 63, 156mg/kg).
3. Studies on chronic toxicity were carried out by intramuscular administration (4, 10, 25, 63, 100mg/kg) to Wistar strain rats for 180 days.
The results of studies are summarized as follows:
1. Acute toxicity of KW-1062 in both mice and rats was less than that of gentamicin. Toxicity varied with species used, and it was ranked in mice>dogs>1062 247 mg/kg and gentamicin 156mg/kg respectively. Main changes observed in subacute toxicity were renal tubular disorder, normocytic anemia and bad general conditions which were due to renal tubular disorder. These changes were observed at above the dose of KW-1062 63mg/kg and gentamicin 25 mg/kg mainly.
3. The changes in chronic toxicity were almost similar to those observed in subacute toxicity, and it was observed at above the dose of KW-1062 25mg/kg mainly.
The toxicological effects observed with KW-1062 were qualitatively similar to those observed with gentamicin and other aminoglycoside antibiotics, and were quantitatively judged to be less toxic than those observed with gentamicin.
