密固达安全使用指南.ppt

Version 11-Sep-07 MA-* Zoledronic Acid: Key Pharmacological Characteristics The unique pharmacologic profile of zoledronic acid may explain why it is possible to achieve profound and sustained suppression of bone resorption with a single, low dose of bisphosphonate: Zoledronic acid has a high binding affinity for bone mineral.1 This maximizes the amount of drug that binds to bone and is likely to minimize the amount of drug that diffuses from bone after binding. Zoledronic acid is a potent inhibitor of FPP synthase.2 This maximizes the antiresorptive potential of the drug and minimizes the total amount of drug required in each dose. Zoledronic acid has a high therapeutic ratio (resorption inhibition:mineralization inhibition)3 and good renal tolerability.4 This maximizes the safety of this bisphosphonate and allows the patient’s total annual dose to be delivered in a single administration. References 1. Nancollas GH, Tang R, Phipps RJ, et al. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006,38:617-627. 2. Dunford JE, Thompson K, Coxon FP, et al. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001;296:235-242. 3. Widler L, Jaeggi KA, Glatt M, et al. Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). J Med Chem. 2002;45:3721-3738. 4. Green JR, Seltenmeyer Y, Jaeggi KA, et al. Renal tolerability profile of novel, potent bisphosphonates in two short-term rat models. Pharmacol Toxicol. 1997;80:225-230. HORIZON-PFT Study 2301 Slide Library V4 3-May-07 CONFIDENTIAL HORIZON-PFT Slide Library - * 输注后3天内发生的最常见不良事件(2%) 总体上，在每次输注后的头3天内，唑来膦酸治疗者中有51.3%发生至少一种AE，而安慰剂组为26.3%。 3天后最常见AE发生率在ZOL和安慰剂组之间无明显差异。 开始于注射后3天内的AE为典型的一过性反应，任一次输注后早期发生的常见AE (≥ 5.0%) 为发热、肌痛、流感样症状、头痛和关节痛。这些AE大部分在3天内缓解（唑来膦酸组的64.71% 和安慰剂组的58.77% ）。7天内