Metabolism of desciclovir, a prodrug of acyclovir, in humans after multiple oral dosing.
Desciclovir (DCV), a prodrug of the antiherpetic agent acyclovir (ACV), is converted in humans to ACV, presumably by xanthine oxidase. Further metabolism of these two compounds was investigated in six human volunteers given 250 mg DCV orally every eight hours for ten days plus one dose on day 11. The mean percent dose recovered in urine (24 hr) on days 2, 5, and 10 as carboxy-DCV (2%) and as carboxy-ACV (14%) along with recoveries of DCV (6%) and ACV (62%) gave a mean total of 84% cleared over a 24-hour period at steady state. Carboxyl metabolites were not found in the plasma of these same subjects at peak DCV concentration on dose day 11. The ratios of DCV and ACV to their corresponding carboxyl metabolites in urine were 4:1 and 3:1, respectively, suggesting that there is little or no difference in the efficiency of these two substrates for oxidation to their carboxylic acid metabolites.
Krasny
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HC
Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
Petty
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BG
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations; D011355:Prodrugs
D004364:Pharmaceutical Preparations; D011355:Prodrugs; C041468:desciclovir; D000212:Acyclovir