9-(2-Phosphonylmethoxyethyl)-2,6-diaminopurine (
PMEDAP) is a broad-spectrum
antiviral agent with potent activity against DNA viruses and retroviruses. We now demonstrate that
PMEDAP is highly efficacious when given orally to mice infected with either Moloney murine sarcoma virus (MSV), Friend
leukemia virus (FLV), or murine cytomegalovirus (MCMV).
PMEDAP markedly delayed MSV-induced
tumor initiation when administered orally at 50, 100, or 250 mg/kg/day during 5 subsequent days. At the highest dose (250 mg/kg/day),
PMEDAP completely prevented
tumor formation in the MSV-infected animals.
PMEDAP also caused 84-96% inhibition of FLV-induced
splenomegaly when given orally to FLV-infected mice at 50-250 mg/kg/day. These
PMEDAP treatment regimens were also markedly effective in increasing the survival rate of MCMV-infected mice. Intraperitoneal
PMEDAP achieved a comparable
antiviral activity at 2- to 5-fold lower doses than oral
PMEDAP. However, the therapeutic index (ratio of the toxic dose to the antivirally effective dose) of oral
PMEDAP was substantially higher than that of intraperitoneal
PMEDAP. Oral
PMEDAP at doses of 100, 250, or 500 mg/kg resulted in plasma
PMEDAP levels of 0.5-2.5 micrograms/ml, which were sustained for 3 or 6 hours after administration and may account for the high
antiviral efficacy achieved.