Dong Betty J
School of Pharmacy, University of California-San Francisco, 521 Parnassus Avenue C-152, San Francisco, CA 94143-0622, USA.
Clin Ther. 2005 Nov;27(11):1725-51. doi: 10.1016/j.clinthera.2005.11.015.
Uncontrolled hyperparathyroidism (HPT), particularly HPT resulting from chronic kidney disease (CKD), is associated with significant morbidity and cardiovascular mortality. Traditional medical therapy (eg, vitamin D sterols, calcium, phosphate binders) has been inadequate for the management of HPT and its vascular and skeletal complications.
: The goal of this article was to review the efficacy and safety profile of cinacalcet, a second-generation calcimimetic, in the management of HPT secondary to CKD, primary HPT, and parathyroid carcinoma.
MEDLINE, Web of Science, and International Pharmaceutical Abstracts were searched from 1995 to July 2005 using the terms cinacalcet, AMG 073, KRN 1493, calcimimetics, hypercalcemia, and hyperparathyroidism.
Compared with placebo, cinacalcet significantly reduced parathyroid hormone levels within 2 to 4 hours after administration (P < 0.05). In Phase III trials involving 1136 patients with secondary HPT, 56% of those who received cinacalcet achieved the National Kidney Foundation Kidney Disease Outcomes Quality Initiative target of a reduction in parathyroid hormone to <300 pg/mL, 65% achieved a calcium-phosphorus product <55 mg2/dL2, and a respective 49% and 46% achieved normalized serum calcium and phosphorus levels (P < 0.001). Cinacalcet's effects were similar regardless of patients' demographic characteristics, duration or mode of dialysis, severity of HPT, or use of concomitant medical therapy. Preliminary evidence suggests that cinacalcet may reverse cortical bone loss. Cinacalcet was well tolerated, with nausea (31%) and vomiting (27%) being the most commonly reported adverse effects. Hypocalcemia was transient in 5% of patients, was usually asymptomatic, and was corrected by dose reduction.
Based on the available evidence, cinacalcet is effective and well tolerated in the treatment of secondary HPT and refractory parathyroid carcinoma. Its use in primary HPT appears promising. Further investigations are needed to determine if cinacalcet can prevent the long-term complications of HPT and reduce mortality.
未控制的甲状旁腺功能亢进症（HPT），尤其是由慢性肾脏病（CKD）导致的HPT，与显著的发病率和心血管死亡率相关。传统医学疗法（如维生素D固醇、钙、磷结合剂）在治疗HPT及其血管和骨骼并发症方面并不充分。
本文的目的是综述第二代拟钙剂西那卡塞在治疗CKD继发性HPT、原发性HPT和甲状旁腺癌方面的疗效和安全性。
使用西那卡塞、AMG 073、KRN 1493、拟钙剂、高钙血症和甲状旁腺功能亢进等检索词，对1995年至2005年7月期间的MEDLINE、科学引文索引和国际药学文摘进行检索。
与安慰剂相比，西那卡塞在给药后2至4小时内显著降低甲状旁腺激素水平（P < 0.05）。在涉及1136例继发性HPT患者的III期试验中，接受西那卡塞治疗的患者中有56%达到了美国国家肾脏基金会肾脏病预后质量倡议中甲状旁腺激素降低至<300 pg/mL的目标，65%的患者钙磷乘积<55 mg2/dL2，分别有49%和46%的患者血清钙和磷水平恢复正常（P < 0.001）。无论患者的人口统计学特征、透析时间或方式、HPT严重程度或是否使用联合药物治疗，西那卡塞的效果均相似。初步证据表明，西那卡塞可能会逆转皮质骨丢失。西那卡塞耐受性良好，最常报告的不良反应是恶心（31%）和呕吐（27%）。5%的患者出现短暂性低钙血症，通常无症状，通过减少剂量可纠正。
根据现有证据，西那卡塞在治疗继发性HPT和难治性甲状旁腺癌方面有效且耐受性良好。其在原发性HPT中的应用似乎很有前景。需要进一步研究以确定西那卡塞是否能预防HPT的长期并发症并降低死亡率。
