mirosamicin and Respiratory-Insufficiency

Acute toxicity studies of miporamicin and its trace ingredients, degradations and metabolites were conducted in mice and rats. 1. Following oral administration of miporamicin (MPM), none died among mice or rats even at the highest dosage levels. Therefore, its LD50 values were estimated to be greater than 2,500 mg/kg for mice and greater than 2,000 mg/kg for rats. The LD50 value of MPM was the highest by oral route, followed, in order, by subcutaneous route and intravenous route. There was no difference in this respect between sexes of animals studied. 2. No signs of abnormalities were observed among mice or rats following oral administration of MPM. In animals dosed with MPM by subcutaneous route, such inflammatory reactions as swelling, subcutaneous hyperemia and hemorrhage, and loss of hair incrustation at the site of injection were noted. Animals among those given MPM by intravenous injection developed postdosing depression of motor activity, respiratory depression or arrest, tremor and convulsion. 3. Deaths from administration of MPM were estimated to be due to paralysis of respiratory function inasmuch as fatally affected animals exhibited respiratory depression and cyanosis and, subsequently, respiratory arrest was followed by cardiac arrest. 4. Trace ingredients, metabolites and degradation products of MPM proved to be essentially the same as MPM in acute toxicities.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Cecum; Female; Injections, Intravenous; Injections, Subcutaneous; Lethal Dose 50; Macrolides; Male; Mice; Mice, Inbred Strains; Organ Size; Rats; Rats, Inbred Strains; Respiratory Insufficiency