Pharmacokinetics and Safety of Bazedoxifene in Hepatically Impaired and Healthy Postmenopausal Women

• Published in: Clinical pharmacology in drug development 2018-05, Vol.7 (4), p.365-372
• Main Authors: McKeand, William, Baird‐Bellaire, Susan, Ermer, James, Patat, Alain
• Format: Article
• Language: English
• Subjects: bazedoxifene; Hormone replacement therapy; Liver; liver disease and metabolism; menopause drug effects; Osteoporosis; osteoporosis prevention and control; Pharmacokinetics; Pharmacology; selective estrogen receptor modulator pharmacology
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.438

Bazedoxifene, a selective estrogen receptor modulator with proestrogenic effects on bone and lipid metabolism and antiestrogenic effects on the breast and endometrium, is a treatment option for osteoporosis in postmenopausal women. It is extensively metabolized by the liver; therefore, a decrease in liver function was expected to decrease bazedoxifene clearance. This single‐dose, open‐label, inpatient/outpatient, nonrandomized study assessed the pharmacokinetics of bazedoxifene 20 mg in 18 postmenopausal women with hepatic impairment and 18 matched healthy postmenopausal women. Bazedoxifene elimination was slower, and exposure was higher, in hepatically impaired subjects compared with healthy subjects. In subjects with severe (Child‐Pugh C) liver impairment, bazedoxifene mean half‐life was 50% longer than that of healthy subjects. Area under the concentration‐time curve geometric mean ratios (90%CI) for Child‐Pugh A, B, and C liver impairment vs healthy subjects were 243% (156‐379), 209% (135‐326), and 368% (236‐572), respectively. Although there were no severe adverse events in this study, bazedoxifene use in patients with hepatic impairment is not recommended.