Byrd R A, Gries C L, Buening M K
Toxicology Research Laboratories, Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, Indiana 46140.
Fundam Appl Toxicol. 1994 Nov;23(4):590-7. doi: 10.1006/faat.1994.1145.
Pregnant CD rats were given vancomycin intravenously in doses of 0, 40, 120, or 200 mg/kg on Gestation Days (GD) 6-15; pregnant New Zealand white rabbits were given 0, 40, 80, or 120 mg/kg intravenously on GD 6-18. Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively. In rats, maternal toxicity was indicated in the 120- and 200-mg/kg treatment groups by cortical tubular nephrosis. Maternal body weight gain and food consumption and fetal viability, weight, and morphology were not adversely affected by vancomycin. Maternal and developmental no observed adverse effect levels (NOAELs) in the rat were 40 and 200 mg/kg, respectively. In rabbits, maternal toxicity was indicated by cortical tubular nephrosis in the 80- and 120-mg/kg treatment groups; a single death and depression of body weight gain and food consumption occurred in the 120-mg/kg treatment group. Developmental toxicity was indicated by depression of fetal weight in the 120-mg/kg treatment group; fetal viability and morphology were not adversely affected by vancomycin. Maternal and developmental NOAELs in the rabbit were 40 and 80 mg/kg, respectively. Based on these data, vancomycin did not exhibit selective toxicity toward the developing rat or rabbit conceptus.
妊娠第6至15天，给妊娠CD大鼠静脉注射剂量为0、40、120或200mg/kg的万古霉素；妊娠第6至18天，给妊娠新西兰白兔静脉注射0、40、80或120mg/kg的万古霉素。分别在妊娠第20天和第28天对大鼠和兔子进行剖宫产。在大鼠中，120mg/kg和200mg/kg治疗组出现皮质肾小管坏死，提示有母体毒性。万古霉素对母体体重增加、食物消耗以及胎儿活力、体重和形态均无不良影响。大鼠母体和发育的未观察到有害作用水平（NOAEL）分别为40mg/kg和200mg/kg。在兔子中，80mg/kg和120mg/kg治疗组出现皮质肾小管坏死，提示有母体毒性；120mg/kg治疗组出现1例死亡，体重增加和食物消耗减少。120mg/kg治疗组胎儿体重降低，提示有发育毒性；万古霉素对胎儿活力和形态无不良影响。兔子母体和发育的NOAEL分别为40mg/kg和80mg/kg。基于这些数据，万古霉素对发育中的大鼠或兔子胚胎未表现出选择性毒性。
