Risedronate Sodium

Risedronate Sodium（利塞膦酸钠，CAS 115436-72-1）是双膦酸盐类药物，核心作用靶点为法尼基焦磷酸合成酶（FPPS，甲羟戊酸途径关键酶），通过抑制该酶阻断破骨细胞异戊烯化脂质合成，进而抑制骨吸收，同时可调控 WNT/β- 连环蛋白信号通路、靶向肺泡巨噬细胞（药物重定位用于肺气肿），与维生素 D3 协同调节骨代谢；活性以骨吸收抑制、骨密度提升及细胞凋亡诱导等功能效应表征；常用应用浓度：细胞实验 0.1~1000 μg/mL（Calu-3 细胞毒性与摄取实验），纳米传递体 / 微球制剂负载浓度对应包封率 86.12%~92.4%，动物实验剂量 0.1 mg/kg/day（口服，骨质疏松模型）、100~200 mg/kg（吸入，大鼠骨松模型）、500 μg/kg/day（气管内给药，肺气肿模型）；临床有效治疗浓度对应多给药方式：口服用于糖皮质激素诱导骨质疏松（GIO）及类风湿关节炎合并 GIO 为每月 75 mg，或每日剂量联合维生素 D3，吸入制剂用于骨质疏松为 0.1 mg/kg/day（RIS）+45 IU/kg/day（VITD3），肺气肿治疗参考 500 μg/kg/day 气管内给药；其生物活性体现为显著提升腰椎骨密度（较安慰剂增加 3.49%）、降低骨转换标志物（TRACP-5b、BAP），诱导肺泡巨噬细胞凋亡以缓解肺气肿，口服生物利用度 < 1%，吸入或纳米制剂可提升生物利用度并减少胃肠道不良反应，安全性良好，适用于骨质疏松及肺气肿的治疗。

参考文献：

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