Clinical Pharmacology of Multiple Doses of Lasofoxifene in Postmenopausal Women

Lasofoxifene, a next‐generation selective estrogen receptor modulator, is undergoing phase 3 clinical development for osteoporosis. This study evaluated daily lasofoxifene for 14 days in healthy postmenopausal women. A loading dose of 5 times the daily dose was followed by daily doses of 0.01 mg ( n = 8), 0.03 mg (n = 8), 0.1 mg ( n = 16), 0.3 mg ( n = 9), 1 mg ( n = 8), or placebo ( n = 16). Samples were collected for pharmacokinetic and pharmacodynamic assessments. Lasofoxifene was well tolerated; study drug—associated adverse events were mild and unrelated to dose. There was a predictable increase in plasma concentrations of lasofoxifene with dose. Pharmacokinetic parameters included mean half‐life of 165 hours, mean area under the plasma concentration‐time curve from time 0 to 24 hours ranging from 1.67 ng•h/mL to 137 ng•h/mL, and mean maximum observed plasma concentration ranging from 0.09 ng/mL to 6.43 ng/mL. Lasofoxifene partially suppressed luteinizing hormone, follicle‐stimulating hormone, low‐density lipoprotein, and N‐telopeptide.