Metabolism of levormeloxifene, a selective oestrogen receptor modulator, in the Sprague-Dawley rat, Cynomolgus monkey and postmenopausal woman

1. The metabolic fate of levormeloxifene in the Sprague-Dawley rat, Cynomol gus monkey and postmenopausal volunteer has been investigated. 2. Two doses of [C-14]levormeloxifene, 0.7 and 50 mg/kg, were given to the male and female rat and monkey, and a single 20-mg dose to the postmenopaus al volunteer. 3. The primary route of excretion in all three species was the faeces. Meta bolism was similar in ail three species, with demethylation forming the maj or metabolite in the rat and postmenopausal volunteer. One of the major met abolites in the monkey involved an oxidative ring opening of a pyrrole ring . 4. The main site of metabolism of levormeloxifene is the liver and the majo rity of the drug and its metabolites is excreted via the faecal route. Meta bolic pathways appear to be similar in the three species studied.