OBJECTIVE: To characterize the pharmacokinetics of the oral, non-estrogen agent 
ospemifene, an estrogen agonist/antagonist with tissue-selective effects (also 
called a selective estrogen receptor modulator) that was recently approved for 
the treatment of dyspareunia associated with vulvar and vaginal atrophy in 
postmenopausal women.
METHODS: Two open-label, Phase 1 studies were conducted to determine the 
pharmacokinetics of ospemifene in healthy postmenopausal women. In the 
single-dose study, 60 mg of [3H]-ospemifene was orally administered to 6 
subjects. Blood, urine, and fecal samples were collected predose and serially up 
to 240 hours postdose. In the multiple-dose study, 12 subjects received 60 mg of 
ospemifene once daily for 9 days. Blood samples were collected predose and 
serially postdose on Day 1, predose on Days 7 and 8, and predose and serially 
postdose on Day 9.
RESULTS: Ospemifene exhibited high plasma protein binding and was extensively 
metabolized, predominantly to 4-hydroxyospemifene and 4'-hydroxyospemifene. In 
the single-dose study, ospemifene was rapidly absorbed, with a median tmax of 
1.50 hours and geometric mean Cmax of 612 ng/ml. The geometric mean (CV%) t1/2 
was 24.5 (21.3) hours and 29.0 (18.0) hours for ospemifene and 
4-hydroxyospemifene, respectively. Fecal elimination accounted for 75% of the 
administered [3H]-ospemifene dose in 240 hours. In the multiple dosing study, 
steady state was reached by Day 7. The mean t1/2 at steady state for ospemifene 
was 29.1 hours. High values for volume of distribution and total clearance 
suggested extensive tissue distribution and efficient elimination of ospemifene.
CONCLUSIONS: In healthy postmenopausal women, ospemifene 60 mg/day reached 
steady state concentrations by Day 7 and showed minimal accumulation of parent 
drug or its two main metabolites, indicating that once daily dosing is 
appropriate.