Reproductive toxicology of fenbufen

The reproductive toxicology of gamma-oxo[1,1-biphenyl]-4-butanoic acid (fenbufen), a new non-steroidal antiinflammatory, analgesic and antipyretic agent was investigated in rats, rabbits and mice after oral administration. This drug showed no evidence of teratogenic or other embryotoxic effects in these three species when administered during organogenesis at dosages as high as 40 mg/kg/day. In male rats no effects on fertility and general reproductive performance were noted except those related to the ulcerogenic effect of this compound. In female rats there were no apparent effects on gonadal function, estrus cycle, mating behavior or fertility. Maternal dystocia and increased mortality of offspring (stillbirths) were observed in rats at doses of 20 mg/kg/d and greater. Increased duration of gestation and prolonged parturition were seen also in rats. Prostaglandin inhibition has been produced in vitro and in vivo by fenbufen and/or its metabolite, biphenyl acetic acid. This suggests that fenbufen shares with other non steroidal antiinflammatory agents the potential for inhibiting prostaglandin-mediated reproductive processes in the human.