新型双膦酸药物-唑来膦酸.ppt

* HORIZON-PFT Study 2301 Slide Library V2 12-Mar-07 CONFIDENTIAL HORIZON-PFT Slide Library - * 由于药物在给药后24小时在血液循环系统浓度较高，因此给药后的3天内一过性不良反应发生率高于安慰剂组，但3天后两组的不良反应发生率相当。 这些不良反应主要包括发热、肌痛、流感样症状、头痛和关节痛。 * 唑来膦酸静脉给药后3天内出现的常见症状（≥5%） 用药后的早发不良事件多数是暂时性的，在开始后的3天内缓解。 所有用药后事件的77% －86% 在开始后的7天内缓解。 如幻灯片显示，常见用药后不良事件的发生率当患者再次用药时，发生率显著降低： 发热， ZOL 5 mg首次用药后发生率为15% ，第二次用药后减为2% ，第三次用药后减少到1%。 肌痛在首次用药后报告为8%，但在第二和第三次ZOL 5 mg用药后发生率降低至1% 流感样症状在首次用药后发生率为7%，第二次用药后为2%，第三次用药后为1% 。 头痛在连续3次用药后的发生率分别为6%、2%和1%。 关节痛在首次、第二次和第三次用药后的发生率分别为5%、2%和1%。 第三次用药后， ZOL 5 mg用药后症状的发生率已与安慰剂组相似。 参考文献 Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822. * 对于常见的给药后一过性症状经过研究证实，使用常用OTC类解热镇痛药物如扑热昔痛、布洛芬可以显著降低患者的体温如图所示。 * 唑来膦酸治疗骨质疏松症疗效总结 快速改善骨转换指标，并持续维持在正常低限水平 全面快速提升骨密度，显著改善骨结构 快速降低各种类型以及各部位骨折风险 降低患者长期死亡率 整体安全性良好 谢谢 * * Functional Domains of Bisphosphonates Bisphosphonates have several functional domains and different molecular structures. As a class, all bisphosphonates work by binding their phosphonate groups to hydroxyapatite. All approved bisphosphonates have and OH group in R1; this creates a triple hook and enhances binding to bone. Varying the R2 substituents can result in differences in antiresorptive potency of several orders of magnitude. Pamidronate and alendronate have an R2 side chain that contains a basic primary nitrogen atom in an alkyl chain and have greater antiresorptive potency than either etidronate or clodronate. Ibandronate has a more highly substituted nitrogen moiety in R2 and shows greater antiresorptive potency than pamidronate or alendronate. The most potent antiresorptive bisphosphonates are risedronate and zoledronic acid, which both contain a nitrogen atom within a heterocyclic ring in the R2 position. Enhancements in antiresorptive potency resulting from differences in the R2 groups appear to be particularly linked to inhibition of the farnesyl pyrophosphate s