Absorption, metabolism, and excretion of [14C]viramidine, a prodrug of ribavirin, were studied in humans following a single oral dose (600 mg). Viramidine was rapidly absorbed, with a time to maximum concentration of the drug in plasma of 1.5 h. Viramidine and ribavirin accounted for only 4.3% and 42% of plasma area under the concentration-time curve (AUC) for radioactivity, respectively, indicating extensive conversion of viramidine to ribavirin, followed by further metabolism of ribavirin. The drug was largely trapped in red blood cells (RBC), with an RBC-to-plasma radioactivity AUC0-infinity ratio of 108. Excretion of total radioactivity in urine and feces accounted for 50.8% and 26.1% of the dose, respectively. The metabolic profile in urine (0 to 24 h) indicated that viramidine was excreted primarily as triazole carboxamide (TCONH2), triazole carboxylic acid nucleoside (TCOOH), and ribavirin with a small amount of unchanged viramidine, which each accounted for 64.1%, 17.0%, 15.7%, and 3.2% of urinary radioactivity, respectively. The amounts of unchanged viramidine (3.4% of dose) and ribavirin (10% of dose) in urine were small after oral administration of viramidine.