2,6-Diamino-9-(2-hydroxyethoxymethyl)purine (
A134U), the 6-deoxy-6-amino analog of the
antiviral agent acyclovir (ACV), was administered orally to dogs and rats. Plasma concentration-time profiles and urinary excretion of
A134U and its deamination product, ACV, were determined. Mean peak plasma ACV concentrations achieved in the dog were 57, 156 and 285 microM after
A134U doses of 20, 50 and 120 mg/kg, respectively, and increased in near proportion to the dose. The urinary recovery of ACV accounted for 60-92% of the two lower doses, but only 40-58% of the highest dose. In the rat, peak plasma ACV concentrations were 3.1 and 10.7 microM, respectively, after 20- and 50-mg/kg doses of
A134U. After 5- and 20-mg/kg oral doses of [2-14C]
A134U, the urinary recovery of ACV (20-27%) accounted for 59 to 76% of the absorbed dose. The remainder was excreted largely as unchanged
A134U, with negligible (0.4-1.3%) biotransformation to inactive metabolites. Except for small decreases in absorption and increases in deamination, no change in the metabolism of
A134U was observed after its repeated
oral administration to rats. Oral dosing of dogs and rats with
A134U resulted in peak plasma concentrations and total urinary recoveries of ACV greater than those observed after equivalent oral doses of ACV, suggesting that
A134U might be an effective
prodrug of ACV for use in the oral
therapy of herpes simplex virus
infections.