[摘要] 继发性甲状旁腺功能亢进(SHPT)是慢性肾脏疾病最常见的并发症之一。度骨化醇是一种选择性维生素D受体激动剂,在肝脏中代谢,对骨骼和肠道的影响较小。度骨化醇主要作用于甲状旁腺,能够有效地抑制全段甲状旁腺激素(iPTH)的分泌,较小程度增加血钙和血磷浓度。度骨化醇被FDA批准用于降低进行性慢性肾透析的SHPT患者的iPTH水平。与骨化三醇相比,高钙血症和高磷血症的发生率低,更加安全有效,是骨化三醇和阿法骨化醇的升级换代产品。
[关键词] 度骨化醇;临床药理学;甲状旁腺激素;临床应用
[Abstract] Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease. Doxercalciferol, which is a selective vitamin D receptor activator is activated in the liver, and has little effect on bone and intestine. Doxercalciferol acts on parathyroid gland, suppress intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. Doxercalciferol has recently been approved by FDA for the reduction of iPTH in haemodialysis patients suffering from SHPT. It demonstrated a lower propensity to cause hypercalcemia and hypercalciuria than calcitriol, and is an alternative to calcitriol.
[Key words] Doxercalciferol; Clinical pharmacology; Parathyroid hormone; Clinical application
1 维生素D类似物作用机制
3 度骨化醇的临床应用
3.1 慢性肾病和继发性甲状旁腺功能亢进症
3.2 其他
Choi等[24]研究了度骨化醇在预防大鼠心肌肥厚中的作用。雄性DSS大鼠在6周龄时开始连续6周喂食高盐饮食。在高盐饮食的前3 d开始,每周3次(周
一、周
三、周五),连续6周给大鼠腹腔注射度骨化醇150 ng。病理及超声心动图结果表明,与高盐饮食大鼠对照组相比,高盐饮食大鼠给药度骨化醇后,心肌肥厚显著减少,心脏功能改善。此外,度骨化醇治疗后,血浆脑钠肽(BNP)水平和组织心房利钠因子(ANF)mRNA水平显著下降。度骨化醇也能显著降低蛋白激酶C-α(PKC-α)水平,表明蛋白激酶C介导的心肌肥大与维生素D缺乏症相关。可见,度骨化醇可以降低大鼠高盐饮食诱发的心肌肥厚及心功能不全。
4 小结
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