Ineffectiveness of adenine arabinoside and adenine arabinoside 5'-monophosphate in simian varicella infection

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Abstract
Adenine arabinoside and adenine arabinoside 5''-monophosphate (ara-AMP) were evaluated for antiviral activity against simian varicella virus infection in monkeys. In a preliminary study for toxicity, i.m. injection of ara-AMP at 15 mg/kg per day as a single injection for 5 days to 2 normal patas monkeys caused no detectable local reaction, no weight loss or changes in serum transaminase levels and no hematological abnormalities. When this dose was given in the treatment of 4 simian varicella virus-infected patas monkeys, no effect was observed on the clinical course of infection, as compared with 4 infected monkeys which received phosphate-buffered saline. Treatment was begun, 43 h after virus inoculation and was continued for 16 days. Toxicity of i.v. administered ara-AMP at 100 or 50 mg/kg per day for 5 days to pairs of uninfected patas monkeys was evident by hematological and hepatic histological alterations, and the death of 1 monkey in each pair. No gross evidence of toxicity occurred in 2 monkeys which received 20 mg of ara-AMP/kg per day. The antiviral efficacy of i.v. treatment was studied in groups of 4 African green monkeys which received adenine arabinoside at 15 mg/kg per day or ara-AMP at 18.4 mg/kg per day. Drug administration began 48 h after inoculation with simian varicella virus and continued for 10 days. The monkeys that received treatment did not respond to infection differently from 4 infected control monkeys similarly treated with phosphate- buffered saline.