Disposition of arildone, an antiviral agent, after various routes of administration

Abstract

[14C]arildone was administered both topically and intravaginally to mice 5 times a day for 7 days to simulate conditions of clinical usage. Urinary and fecal excretion of radioactivity indicated that arildone was extensively absorbed by both routes of administration. The levels of radioactivity in the vagina and skin declined from about 12 micrograms equivalents per g to 3 micrograms equivalents per g between 1 and 2 days after the last application. Only small amounts of unchanged arildone were found in urine from the vaginally treated animals; the major urinary metabolites were chloromethoxyphenol, its sulfate ester, and chlorohydroquinone sulfate. After about 1 month of daily oral administration of arildone to rats and monkeys or vaginal administration three times a day for 20 days to dogs, only low levels of intact drug were found in the systemic circulation. The disposition or beta-phase half-life of arildone in monkeys after intravenous administration was about 0.5 h. The disposition of [14C]arildone in mice, rats, dogs, and monkeys after various routes of administration was also investigated.