PRECLINICAL TOXICOLOGY STUDIES WITH ACYCLOVIR - TERATOLOGIC, REPRODUCTIVE AND NEONATAL TESTS
PRECLINICAL TOXICOLOGY STUDIES WITH ACYCLOVIR - TERATOLOGIC, REPRODUCTIVE AND NEONATAL TESTS
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DOI：
10.1016/s0272-0590(83)80105-5
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
TUCKER, WE
中科院分区：
文献类型：
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作者：
MOORE, HL;SZCZECH, GM;TUCKER, WE
阿昔洛韦致畸、生殖和新生儿试验的临床前毒理学研究。摩尔，H. L.，小的，Szczech，G.M.，Rodwell，D.E.，卡普，R.W.，小的，de米兰达，P.和塔克，W.E.，Jr.（1983）. Fundamental.应用毒理学3：560-568。进行了五项研究，以确定阿昔洛韦（ACV），一种新的核苷类似物的抗病毒化疗，对实验动物的生殖和发育产生不良影响的潜力。在一项两代生殖/生育力研究中，以50、150和450 mg/kg/天的剂量对F0代小鼠进行灌胃给药时，ACV未产生不良反应。对一些小鼠进行了致畸作用评价，对另一些小鼠进行了出生后发育（包括行为）评价，结果为阴性。在主要器官形成期间，以12、25和50 mg/kg/天的剂量水平皮下注射给孕鼠和孕兔，无环鸟苷没有胚胎毒性，也没有增加胎儿畸形的发生率。一项比较LD 50的研究表明，3日龄大鼠对ACV的急性毒性作用并不比成年大鼠更敏感。最后，在一项多剂量综合毒性研究中，以5、20和80 mg/kg/天剂量对新生大鼠皮下注射ACV，连续19天。20 mg/kg/天剂量组新生儿的体重增量受影响极小，80 mg/kg/天剂量组新生儿的体重增量显著降低。在80 mg/ kg/天剂量下发生了极轻微的肾脏病变，但未观察到对发育中的器官系统产生不良影响的其他体征。除了80毫克/千克/天剂量组新生大鼠体重增加减少外，在各种临床前毒理学研究中，ACV未对哺乳动物发育产生不良影响。
Preclinical Toxicology Studies with Acyclovin Teratologic, Reproductive and Neonatal Tests. Moore, H.L., Jr., Szczech, G.M., Rodwell, D.E., Kapp, R.W., Jr., de Miranda, P. and Tucker, W.E., Jr. (1983).Fundam. Appl Toxicol3:560–568. Five studies were done to define the potential of Acyclovir (ACV), a new nucleoside analog for antiviral chemotherapy, to produce adverse effects on reproduction and development in laboratory animals. ACV produced no adverse effects when given by gavage to F0generation mice at 50, 150 and 450 mg/kg/day in a two generation reproduction/fertility study. Some mice were evaluated for teratologic effects and others for postnatal development, including behavior, with negative results. ACV was not embryotoxic and did not increase the incidence of fetal malformations when given by subcutaneous injection to pregnant rats and rabbits at dose levels of 12, 25 and 50 mg/kg/day during the periods of major organogenesis. A comparative LD50study revealed that 3-day-old rats were not more sensitive to acute toxic effects of ACV than more mature rats. Finally, in a comprehensive multidose toxicity study ACV was given subcutaneously to neonatal rats at 5, 20 and 80 mg/kg/day for 19 consecutive days. There was minimal effect on body weight gain in neonates treated at 20 mg/kg/day and a significant decrease in body weight gain at 80 mg/kg/day. Minimal renal lesions occurred at 80 mg/ kg/ day but no other signs of adverse effects on developing organ systems were observed. Except for decreased body weight gain in neonatal rats treated at 80 mg/kg/day, ACV did not produce adverse effects on mammalian development when tested in a variety of preclinical toxicology studies.