Pharmacological studies on 5-methoxymethyl-2'-deoxyuridine: a new antiviral agent

Pharmacokinetic and pharmacodynamic properties of 5-methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity against herpes simplex virus, were investigated. After i.v. administration of [2-14C]MMUdR at 50 and 25 mg/kg to rats, the overall half life of the drug (T 1/2 Kel) was calculated to be 32 to 35 min. The biological half life of the drug (T 1/2 beta) was 89 min and the distribution half life (T1/2 alpha) was 6 min. The specific volume of distribution was calculated to be 1.28 to 1.35 liters/kg and the total body clearance rate of the drug was 10 ml/min/kg. The data were analyzed on the basis of a two-compartment open pharmacokinetic model. After i.p. administration of 50 mg/kg of [2-14C]MMUdR to mice, peak plasma levels of 35.6 micrograms/ml were attained in 10 min. The highest tissue concentrations of [2-14C]MMUdR in mice were 63 micrograms/g in kidneys (30 min) followed by 36 micrograms/g in liver and spleen and 30 to 32 micrograms/g in lungs and gut (20 min). MMUdR did not undergo biotransformation in plasma but urine was found to contain MMUdR (greater than 80%) and a small amount of radioactivity which comigrated with MMUdR monophosphate. Administration of 500 mg/kg of MMUdR i.v. to New Zealand White rabbits did not produce any observable effects on the heart rate, ECG pattern or respiration rate. Vasodilation of 39-sec duration was observed immediately after administration of MMUdR.