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A Single‐Dose Pharmacokinetic Study of Lasofoxifene in Healthy Volunteers and Subjects With Mild and Moderate Hepatic Impairment
Author(s) -
Bramson Candace,
Ouellet Daniele,
Roman Doina,
Randinitis Edward,
Gardner Mark J.
Publication year - 2006
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 - 10.1177/0091270005283278
Subject(s) - pharmacokinetics , confidence interval , medicine , gastroenterology , area under the curve
Lasofoxifene, a selective estrogen receptor modulator for osteoporosis management, is metabolized primarily by hepatic oxidation and conjugation. This study compared the pharmacokinetics of 0.25 mg lasofoxifene in subjects with mild (Child‐Pugh grade A, n = 6) or moderate (Child‐Pugh grade B, n = 6) hepatic impairment and healthy volunteers ( n = 6). Analysis of variance was used to calculate 90% confidence intervals for the ratios (impaired/healthy) of least squares mean log maximum plasma concentration (C max ) and area under the curve (AUC) values. Lasofoxifene pharmacokinetics was similar between healthy and mild hepatic impairment subjects: ratios of C max and AUC from 0 to infinity (AUC [0‐∞] ) were 101% (75.0–138) and 95.5% (77.9–117), respectively. In subjects with moderate hepatic impairment, ratios of C max and AUC [0‐∞] were 121% (89.6–165) and 138% (112–169), respectively; mean terminal half‐life was 252 hr compared to 193 hr in healthy subjects. Dose adjustment should not be required for subjects with mild to moderate hepatic impairment.