The disposition of [3H]zeranol has been studied in the female Wistar rat, New Zealand rabbit, beagle dog, rhesus monkey and man. The blood elimination half-life of total radioactivity in rabbit was 26 h, monkey 18 h and man 22 h. In all species studied the drug was absorbed, oxidized and/or conjugated, and was extensively excreted via the bile in all species except rabbit and man, in which urinary excretion predominated. Blood total radioactivity in man probably consisted entirely of conjugates of zeranol and/or its metabolites. Urinary metabolites in all species included conjugates (beta-glucuronides and/or sulphates) of zeranol and the major metabolite zearalanone. A more polar minor metabolite was isolated from human urine and was shown to be hydroxy-zeranol. Taleranol (7 beta-zearalanol, the lower-melting diastereoisomer), a probable metabolite of zeranol (7 alpha-zearalanol, the higher-melting diastereoisomer) in animals and in man, was shown to be a urinary metabolite in a female New Zealand white rabbit which had received [3H]zeranol (8 mg/kg per day) for seven days. A reverse isotope dilution method was developed for the quantification of both diastereoisomers of zearalanol, and also zearalanone, in urine.

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Summary. The synthesis of 2,4,6-~ycloheptatrienethione (1) was accomplished by reaction of tropone and phosphorus pentasulfide. Although 1 proved to be extremely unstable in concentrated solution, its UV. spectrum was measured, the &-values being determined indirectly by hydrolysis'to tropone. The proof of structure rests on analytical data, conversion to tropone oxime on reaction with hydroxylamine and reaction with the sodium salt of malonitrile t o give 2-amino-3-cyano-3aH-cyclohepta[b]thiophene (4) which rearranged on chromatography to give what is probably the corresponding 8H-compound (5). On dissolving 1 in 95% sulfuric acid, a large hypsochromic shift in the UV. spectrum was observed, which may be due to the mercaptotropylium ion.