Inhibitory effect of FK-565 alone and in combination with zidovudine on retroviral infection by Friend leukemia virus in mice.

Abstract

The effects of route and starting time of administration on FK-565 inhibition of splenomegaly by Friend leukemia virus (FLV) were studied in mice, and the concomitant effect of FK-565 in allowing reduction of zidovudine dosage was estimated. FK-565 inhibited splenomegaly in intravenous and oral doses of 0.01 to 1 mg/kg, but time of initial dosing had little effect on this inhibition. When 0.01 or 1 mg/kg of FK-565 was given intravenously with intraperitoneal doses of 0.63, 2.5, 10 and 40m g/kg of zidovudine, the inhibition rate of splenomegaly at all doses was markedly and dose-dependently higher than when either drug was given alone, and the concomitant use of FK-565 with zidovudine enabled a 16-fold reduction of the dose of zidovudine. The survival rate and survival time after infection with massive amounts of FLV were higher when FK-565 1 mg/kg and zidovudine 20 mg/kg were given in combination than when either drug was given alone. Inhibition of FLV splenomegaly was reflected in the prolonged survival time of the infected mice.