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The pharmacokinetics of pradefovir and adefovir, 9-(2-phosphonylmethoxyethyl) adenine (PMEA), was evaluated in healthy male volunteers after oral dosing of pradefovir (10, 30, or 60 mg). Pradefovir was absorbed rapidly. The maximum serum concentration, the area under the concentration-time curve between 0 and 96 hours after dosing (A UC0–96), and the area under the plasma concentration versus time curve from time 0 to infinity (AUC0-∞) of pradefovir and PMEA increased with the dose of pradefovir. The ratio of PMEA to pradefovir for AUC0–96 and AUC0∞ ranged from 1.4 to 1.8. Renal clearance of pradefovir (18–31 L/h) increased with the dose of pradefovir and was greater than glomerular filtration. The fraction of total body clearance due to renal clearance was low (0.045 to 0.083), suggesting that metabolic clearance played a significant role in the clearance of pradefovir in man. In addition, an evaluation of the food effect was conducted at the 30-mg dose. The results indicate that food intake has no effect on the extent of exposure of pradefovir and PMEA but may decrease the rate of systemic availability of PMEA.