Absorption, metabolism, and excretion of ( 3 H)‐ospemifene following a single oral dose to post‐menopausal women

Background/Aims Ospemifene is a novel selective oestrogen receptor modulator being developed for osteoporosis. The aims were: to evaluate the pharmacokinetics of total radioactivity, unchanged ospemifene, and the major metabolite 4‐hydroxyospemifene; to obtain mass balance by quantifying the urinary and faecal excretion of radioactivity; to examine the pattern of metabolites in plasma, urine and faeces and the ex‐vivo plasma protein binding of total radioactivity and ospemifene. Methods A single oral dose (60 mg) of ospemifene, containing 20.2 MBq ( 3 H)‐ospemifene, was administered orally to 6 healthy post‐menopausal women. Blood, urine and faeces sampling was performed up to 240h post‐dose. Results/Conclusions Ospemifene was rapidly absorbed (t max 0.75–3 h) and steadily eliminated (t 1/2 of 25–29 h). 4‐hydroxyospemifene underwent formation rate‐limited elimination with t max similar to the parent drug. Radioactivity was mainly faecally eliminated, with 75% of the dose being recovered over 240h, with 7% eliminated in urine. Ospemifene and total drug‐related material were extensively plasma protein bound (93–98%) with minimal binding to blood cells. Ospemifene metabolism was extensive with several radiolabelled metabolites in plasma, urine and faeces. Clinical Pharmacology & Therapeutics (2005) 77 , P82–P82; doi: 10.1016/j.clpt.2004.12.205