1140 THE EFFECT OF AN ANTIVIRAL AGENT (WIN 51,711) ON COXSACKIEVIRUS A9 INFECTION IN SUCKLING MICE

Abstract

WIN 51,711 is an antiviral agent with demonstrated in vitro activity against a number of Picornaviruses, including Coxsackievirus A9 (CA9). The drug has proved to be effective in animal model studies against Echovirus 9 and Poliovirus 2 infection in mice. This study used white Swiss mice which were infected with CA9 when they were between 24 and 48 hours of age. The LD50 for these mice was established as 1.8 × 105 TCID, and this quantity of virus was injected intraperitoneally (ip). Several routes of delivery of the drug have been tested. Giving 100 mg/kg/day of the drug in a 1% gum tragacanth suspension as a single daily ip injection led to significent delay in weight gain and mortality approaching 50%. Reducing this dose to 50 mg/kg/day ip appeared to alleviate this problem, as did delivering 100 mg/kg/day subcutaneously instead of ip. In the limited numbers of mice studied to date, protection against mortality using the latter two routes is 100%. Administering 100 mg/kg/day po once daily in a 1% gum tragacanth suspension had no effect on animal growth, but also provided no protection against mortality or symptomatology. It is hypothesized that this lack of effect reflects either poor absorption via the po route in suckling mice, or the shorter half-life of the drug when administered in oral boluses instead of ip or subcutaneous deposition. The toxicity of the 100 mg/kg/day dose ip appeared to be mechanical, since eventually crystals could be seen to accumulate in the peritoneum.