Abstract
1. The metabolic fate of levormeloxifene in the Sprague-Dawley rat, Cynomolgus monkey and postmenopausal volunteer has been investigated. 2. Two doses of [14C] 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 postmenopausal volunteer. 3. The primary route of excretion in all three species was the faeces. Metabolism was similar in all three species, with demethylation forming the major metabolite in the rat and postmenopausal volunteer. One of the major metabolites 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 majority of the drug and its metabolites is excreted via the faecal route. Metabolic pathways appear to be similar in the three species studied.
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