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.
Roman
Doina
D
Pfizer Inc, Ann Arbor, Michigan, USA.
Bramson
Candace
C
Ouellet
Daniele
D
Randinitis
Edward
E
Gardner
Mark
M
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004077:Digoxin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011759:Pyrrolidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; C111332:Lasofoxifene; D004077:Digoxin