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Effect of Lasofoxifene on the Pharmacokinetics of Digoxin in Healthy Postmenopausal Women
Author(s) -
Roman Doina,
Bramson Candace,
Ouellet Daniele,
Randinitis Edward,
Gardner Mark
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005282627
Subject(s) - digoxin , pharmacokinetics , medicine , pharmacology , postmenopausal women , heart failure
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 .