Preclinical Toxicology Studies with Acyclovir: Teratologic, Reproductive and Neonatal Tests

Preclinical Toxicology Studies with Acyclovin Teratologic, Reproductiveand 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 Toxicol 3:560–568. Five studies weredone to define the potential of Acyclovir (ACV), a new nucleosideanalog for antiviral chemotherapy, to produce adverse effectson reproduction and development in laboratory animals. ACV producedno adverse effects when given by gavage to F₀ generation miceat 50, 150 and 450 mg/kg/day in a two generation reproduction/fertilitystudy. Some mice were evaluated for teratologic effects andothers for postnatal development, including behavior, with negativeresults. ACV was not embryotoxic and did not increase the incidenceof fetal malformations when given by subcutaneous injectionto pregnant rats and rabbits at dose levels of 12, 25 and 50mg/kg/day during the periods of major organogenesis. A comparativeLD₅₀ study revealed that 3-day-old rats were not more sensitiveto acute toxic effects of ACV than more mature rats. Finally,in a comprehensive multidose toxicity study ACV was given subcutaneouslyto neonatal rats at 5, 20 and 80 mg/kg/day for 19 consecutivedays. There was minimal effect on body weight gain in neonatestreated at 20 mg/kg/day and a significant decrease in body weightgain at 80 mg/kg/day. Minimal renal lesions occurred at 80 mg/kg/ day but no other signs of adverse effects on developingorgan systems were observed. Except for decreased body weightgain in neonatal rats treated at 80 mg/kg/day, ACV did not produceadverse effects on mammalian development when tested in a varietyof preclinical toxicology studies.