Abstract
The distribution, metabolism and excretion of bifluranol, a novel bibenzyl, has been determined in mouse, rat, ferret and dog and compared to the fate of diethylstilboestrol. Bifluranol is extensively absorbed, but systemic tissue levels are low due to hepatic uptake and biliary excretion. After enterohepatic recirculation the dose is excreted in the faeces and only small amounts appear in urine. This pattern is similar to that reported for diethylstilboestrol. The metabolic fate of bifluranol was found to differ considerably from that of diethylstilboestrol. In rat oxidative metabolism of bifluranol (4-8%) was considerably lower than that reported for diethylstilboestrol (30%). Bifluranol was extensively excreted as diconjugates with glucuronic acid and sulphate, in contrast to the major conjugate of diethylstilboestrol, the monoglucuronide. Preliminary data indicate conjugation of bifluranol with phosphate in ferret and dog. Glucuronyl- and sulpho-transferase enzyme systems were shown to conjugate both bifluranol and diethylstilboestrol. The rate of bifluranol conjugation in both systems was >ten-fold higher than with diethylstilboestrol and may explain in part the extensive diconjugate formation of bifluranol. The differences in metabolism of bifluranol and diethylstilboestrol are discussed in terms of the aromatic fluorine substituents of bifluranol.