Pharmacokinetics (PK) and pharmacodynamics (PD) of daily lasofoxifene (LASO) in Japanese (J) and Caucasian (C) postmenopausal (PM) women

Background LASO, a next generation selective estrogen receptor modulator (SERM), is in late development for the treatment of osteoporosis. It is oxidatively and conjugatively metabolized. Since ethnic differences in drug metabolism exist, potential PK/PD differences for LASO in J and C PM women were explored. Methods Two randomized, investigator blind, parallel-group studies were run in PM women. The study in J subjects was placebo-controlled, whereas the study in C subjects was not. Daily 0.25, 0.5 mg or placebo tablets were given for 14 days, with loading doses of 8-times the daily dose given on day 1. Nine subjects were treated at each active dose level, with six J subjects treated with placebo. Plasma/serum samples were collected during and following treatment for PK/PD evaluations. Results The PK/PD of LASO were similar in J and C subjects. Exposure increased predictably with dose, with a mean T1/2 of approximately 150 hours. LDL concentrations generally decreased with LASO treatment, whereas HDL was not consistently affected. LASO was well-tolerated. Conclusions Following daily dosing for 14 days, there do not appear to be significant differences in LASO PK/PD/safety between J and C populations at clinically relevant doses. Clinical Pharmacology & Therapeutics (2005) 77, P83–P83; doi: 10.1016/j.clpt.2004.12.209