© 1983 Oxford University Press
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Preclinical Toxicology Studies with Acyclovir: Carcinogenicity Bioassays and Chronic Toxicity Tests
Wellcome Research Laboratories 3030 Cornwallis Road, Research Triangle Park, NC 27709
Preclinical Toxicology Studies with Acyclovir: Carcinogenicity Bioassays and Chronic Toxicity Tests. Tucker, W.E., Jr., Krasny, H.C., de Miranda, P., Goldenthal, E.I., Elion, G.B., Hajian, G. and Szczech, G.M. (1983). Fundam. Appl. Toxicol. 3:579–586. Acyclovir (ACV), a nucleoside analog that is a new herpes-specific antiviral drug, was given by gavage at 50, 150 and 450 mg/kg/day to Sprague Dawley rats and Swiss mice for most of their lifetime to assess chronic toxicity and carcinogenicity. Treatment with ACV did not shorten the lifespan of either rats or mice. In fact, female mice given 150 and 450 mg/kg/day had significantly longer mean durations of survival than control female mice when analyzed by the life table technique. There were no signs of toxicosis produced by chronic exposure to ACV in either the rats or mice, and there was no drug-related increase in neoplasms in either species. Four groups of Beagle dogs were initially given daily oral doses of 15, 45 or 150 mg/kg ACV in a 1 year chronic toxicity study. Dogs treated at 150 mg/ kg/day vomited, had diarrhea, consumed less feed and lost weight within 2 weeks. Dogs treated at 45 mg/kg/day also had minimal signs of gastrointestinal toxicosis. These dose levels were then decreased to 60 and 30 mg/kg/day for the rest of the one year test period. With the exception of occasional and inconsistent emesis and diarrhea, the 60 mg/kg/day dose level was well tolerated. Some mid and high dose dogs had sore paws due to erosion of footpads and cracking, splitting and loosening of the nails first becoming evident during the 13th week of the study. Several of these dogs subsequently lost the keratin from some claws. There was nail regeneration and healing of footpads as the study progressed, with all claws appearing essentially normal at the end of 1 year. Nails and footpads of dogs given 15 mg/kg/day were normal throughout the study.