METABOLISM OF DROLOXIFENE IN THE CD-1 MOUSE, FISCHER-344 RAT AND CYNOMOLGUS MONKEY

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