Tucker W E, Macklin A W, Szot R J, Johnston R E, Elion G B, de Miranda P, Szczech G M
Fundam Appl Toxicol. 1983 Nov-Dec;3(6):573-8. doi: 10.1016/s0272-0590(83)80107-9.
Acyclovir (ACV), a new antiherpes drug, was evaluated for toxicity in a series of acute and subchronic toxicity tests. Oral LD50 values were greater than 10 000 mg/kg in male ICR mice and greater than 20 000 mg/kg in male Long Evans rats. When ACV was given iv, the LD50 was 405 mg/kg for male mice and greater than 600 mg/kg for male rats. Additionally, LD50 values for male rats treated sc were 1070, 790, 678, and 650 mg/kg in rats that were respectively, 3, 10, 28 and 71 days old indicating that very young rats were not more sensitive to acute toxic effects of ACV. There were no signs of toxicosis in CD-1 mice given ACV by gavage at dose levels of 50, 150 and 450 mg/kg/day for 1 month. Obstructive nephropathy occurred in rats given 20, 40 and 80 mg/kg/day once each day by rapid iv injection for 3 weeks. Both 5 and 10 mg/kg/day were no effect dose levels. Renal damage caused by precipitation of drug crystals in renal tubules and collecting ducts in rats given ACV by rapid iv injection was readily reversible within 2 weeks. Beagle dogs were given doses of 10, 20, 25, 50 and 100 mg/kg b.i.d. by rapid iv injection for 1 month. All 8 dogs given 100 mg/kg b.i.d. died by the 8th day of treatment; 5 of 8 dogs given 50 mg/kg b.i.d. died after 21 to 31 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
阿昔洛韦（ACV）是一种新型抗疱疹药物，在一系列急性和亚慢性毒性试验中对其毒性进行了评估。雄性ICR小鼠口服半数致死量（LD50）值大于10000毫克/千克，雄性长爪沙鼠口服LD50值大于20000毫克/千克。静脉注射阿昔洛韦时，雄性小鼠的LD50为405毫克/千克，雄性大鼠的LD50大于600毫克/千克。此外，皮下注射给药的雄性大鼠的LD50值分别为1070、790、678和650毫克/千克，这些大鼠分别为3日龄、10日龄、28日龄和71日龄，表明幼龄大鼠对阿昔洛韦的急性毒性作用并非更敏感。给予CD-1小鼠灌胃阿昔洛韦，剂量为50、150和450毫克/千克/天，持续1个月，未出现中毒迹象。给予大鼠每天一次快速静脉注射20、40和80毫克/千克/天，持续3周，出现梗阻性肾病。5和10毫克/千克/天为无作用剂量水平。快速静脉注射阿昔洛韦导致大鼠肾小管和集合管中药物晶体沉淀引起的肾损伤在2周内易于逆转。比格犬每天两次快速静脉注射剂量为10、20、25、50和100毫克/千克，持续1个月。所有接受100毫克/千克/天两次注射的8只犬在治疗第8天死亡；接受50毫克/千克/天两次注射的8只犬中有5只在治疗21至31天后死亡。（摘要截断于250字）
