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Dosing time-dependent influence of raloxifene on plasma plasminogen activator inhibitor-1 concentration in postmenopausal women with osteoporosis.
MedLine Citation:
PMID:  23323567     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Raloxifene, a selective oestrogen receptor modulator commonly used for the treatment of postmenopausal osteoporosis, affects the coagulation and fibrinolytic systems and consequently increases the risk of venous thromboembolism. Because both the coagulation and fibrinolytic systems exhibit circadian rhythms, we aimed to investigate the influences of dosing time of raloxifene on markers of coagulation and fibrinolysis, as well as on bone metabolic markers. Thirty-nine postmenopausal patients with osteoporosis were randomly allocated to two groups: one received 60-mg raloxifene once daily in the morning and the other in the evening, for 12 months. In both groups, activities of coagulation factors IX and XII were significantly increased after 12 months of treatment compared with baseline. Activities of coagulation factors II and V, and levels of the bone metabolic markers bone alkaline phosphatase and tartrate-resistant acid phosphatase 5b, decreased in both groups. The changes in these markers were not different between the groups. By contrast, the plasma concentration of plasminogen activator inhibitor-1 increased in the morning-dose group [mean percentage change 40.9 (95% confidence interval 9.4, 72.5)], but not in the evening-dose group [-0.3 (-31.5, 30.9)], and these percentage changes differed significantly (P<0.05) between the groups. Because an elevated concentration of plasminogen activator inhibitor-1 is known to be associated with the risk of venous thromboembolism, this study suggests that the dosing time of raloxifene influences its safety. Further larger-scale studies are needed to determine the clinical usefulness of chronotherapy with raloxifene. © 2013 The Authors Clinical and Experimental Pharmacology and Physiology © 2013 Wiley Publishing Asia Pty Ltd.
Authors:
Hitoshi Ando; Toshiki Otoda; Hitoshi Ookami; Yukihiro Nagai; Akihiro Inano; Toshinari Takamura; Kentarou Ushijima; Keiko Hosohata; Eiki Matsushita; Tetsuo Saito; Shuichi Kaneko; Akio Fujimura
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors Clinical and Experimental Pharmacology and Physiology © 2013 Wiley Publishing Asia Pty Ltd.
Affiliation:
Division of Clinical Pharmacology, Department of Pharmacology, School of Medicine, Jichi Medical University, Shimotsuke, Japan.
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