Effect of Lasofoxifene on the Pharmacokinetics of Digoxin in Healthy Postmenopausal Women

Lasofoxifene is in late‐stage development for the prevention and treatment of osteoporosis. Digoxin is commonly prescribed for arrhythmias and congestive heart failure, has a narrow therapeutic index, and may be coadministered with lasofoxifene. This study was conducted to determine the effect of lasofoxifene (4‐mg loading dose on day 11 followed by 0.5 mg/d on days 12–20) on the steady‐state pharmacokinetics of digoxin (0.25 mg/d on days 1–20) in 12 healthy postmenopausal women. On days 10 and 20, blood and urine samples were collected for 24 hours to determine digoxin concentrations. The 90% confidence interval (CI) of least squares mean ratio for maximum concentration (C max ) and area under the plasma concentration‐time curve (AUC) was calculated. Lasofoxifene had no effect on digoxin plasma pharmacokinetics with a ratio (90% CI) of 95.4% (84.6%–107%) and 103% (97.7%–108%) for C max and AUC 0–24 , respectively. The ratio of the percentage of dose eliminated unchanged in urine in 24 hours was 127% (116% to 142%). Coadministration of lasofoxifene had no effect on the steady‐state pharmacokinetics of digoxin .