文章基本信息

标题：Osteotropic Drug Delivery System (ODDS) Based on Bisphosphonic Prodrug. V. Biological Disposition and Targeting Characteristics of Osteotropic Estradiol
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作者：Jiro FUJISAKI ; Yuji TOKUNAGA ; Toshiya TAKAHASHI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1997
卷号：20
期号：11
页码：1183-1187
DOI：10.1248/bpb.20.1183
出版社：The Pharmaceutical Society of Japan
摘要：An osteotropic drug delivery system (ODDS) based on a bisphosphonic prodrug has been developed for 17β-estradiol (E₂) to improve patient compliance in estrogen replacement therapy of postmenopausal osteoporosis. The biological disposition and the targeting efficiency of a bisphosphonic prodrug of E₂, disodium [17β-(3'-hydroxy-1', 3', 5'-estratrienyloxy)carbonylpropyl carboxamidomethylene]bisphosphonate (E₂-BP), was investigated in ovariectomized rats. After intravenous injection, E₂-BP was rapidly taken up into the bone and subsequently cleared from the bone at a half-life of 13.5d. The bone concentration of regenerated E₂ was maintained throughout 28d. In contrast, E₂ injected intravenously showed extremely low bone distribution and rapid clearance from the bone, and E₂ administered orally showed even lower bone distribution. Therapeutic availability (TA) and drug targeting index (DTI), which were calculated on the basis of the AUCs for E₂ in the bone and plasma after injection of E₂-BP and E₂, were 64.6 and 451, respectively. These results suggest that ODDS has a potential to improve not only the apparent potency but also the therapeutic index of E₂. As compared with the conventional estrogenic products, E₂-BP should improve patient compliance with lower adverse effects and less frequent medication in long-term estrogen replacement therapy.
关键词：estradiol;osteotropic drug delivery system;prodrug;bone;drug targeting index;therapeutic availability