Metabolism of droloxifene in the CD-1 mouse, Fischer-344 rat and cynomolgus monkey

1. The fate of [14C]droloxifene, a novel non-steroidal anti-oestrogen, was studied following oral administration to the CD-1 mouse, F-344 rat and Cynomolgus monkey. 2. Most of the radioactivity was primarily excreted in the faeces and urine was the minor route of excretion. 3. Droloxifene was extensively metabolized in all three species, primarily by two metabolic pathways; glucuronidation of unchanged droloxifene and oxidative metabolism, presumably by cytochrome P450. 4. In mouse, oxidative metabolism followed by conjugation played a significant role in the elimination of droloxifene. An unusual diglucuronide of 4-hydroxydroloxifene was also identified in this species. 5. In rat, glucuronidation and oxidative metabolism were significant, whereas in monkey glucuronidation of droloxifene was the predominant pathway of elimination.