Gol'dberg L E, Filippos'iants S T, Belova I P, Vertogradova T P, Shepelevtseva N G
Antibiotiki. 1979 Jan;24(1):60-7.
The LD50 of tobramycin sulphate administered intravenously, intraperitoneally, subcutaneously and orally to albino mice was 77 (73--82), 262 (234--294), 560 (500--627) and greater than 10500 mg/kg respectively. With an increase in the rate of intravenous administration tobramycin toxicity increased. When tobramycin sulphate was administered subcutaneously daily in multiple doses equivalent to the daily therapeutic doses from humans (calculated for the body surface) and in the doses 2--3 times higher than the above therapeutic ones, the function of the kidneys, liver and the Preier's reflex did not significantly change. When the doses were 8--10 times higher than the therapeutic ones, an increase in the urea level in the blood serum, disappearance and a decrease in the Preier's reflex were observed. The impairment of the kidney function was accompanied by degenerative changes in the convoluted tubules of the kidneys, ischemia of the renal glomeruli and appearance of protein secretion in their capsule cavities. The picture of the peripheral blood did not suffer significant changes. The studies on the acute and chronic toxicity of tobramycin sulphate prepared at the Institute of New Antibiotics showed that the drug did not differ from the import tobramycin samples.
硫酸妥布霉素经静脉、腹腔、皮下及口服给予白化小鼠的半数致死量分别为77（73 - 82）、262（234 - 294）、560（500 - 627）及大于10500毫克/千克。随着静脉给药速率的增加，妥布霉素的毒性增强。当以相当于人类每日治疗剂量（按体表面积计算）的多剂量以及高于上述治疗剂量2 - 3倍的剂量每日皮下给予硫酸妥布霉素时，肾脏、肝脏功能及普莱尔反射均未发生显著变化。当剂量高于治疗剂量8 - 10倍时，观察到血清尿素水平升高、普莱尔反射消失及减弱。肾功能损害伴有肾小管的退行性改变、肾小球缺血及其囊腔内出现蛋白质分泌。外周血情况未发生显著变化。新抗生素研究所制备的硫酸妥布霉素的急性和慢性毒性研究表明，该药物与进口妥布霉素样品无异。
