1,25-二羟-16-烯-23-炔维生素D3可减轻尿毒症大鼠的继发性甲状旁腺功能亢进，且对血钙影响较小。

1,25-(OH)2-16ene-23yne-D3 reduces secondary hyperparathyroidism in uremic rats with little calcemic effect.

作者信息

Lippuner Kurt, Perrelet Romain, Casez Jean-Paul, Popp Albrecht, Uskokovic Milan R, Jaeger Philippe

机构信息

Osteoporosis Unit/Policlinic of Medicine, University Hospital of Berne, Berne, Switzerland.

出版信息

Horm Res. 2004;61(1):7-16. doi: 10.1159/000075191. Epub 2003 Nov 27.

DOI:10.1159/000075191

PMID:14646396

Abstract

OBJECTIVES

To compare the effects of vitamin D analogs versus calcitriol on serum levels of Ca, P and parathyroid hormone (PTH). A compound better than calcitriol should increase the Ca x P product less than calcitriol for an equivalent decrease in PTH levels.

METHODS

Biological activity of 4 vitamin D analogs, 1,25-(OH)(2)-16ene- D(3) (RO(1)), 1,25-(OH)(2)-16ene-23yne-D(3) (RO(2)), 1,25-(OH)(2)-26,27-hexafluoro-16ene-23yne-D(3) (RO(3)) and 1,25-(OH)(2)-16ene-23yne-26,27-hexafluoro-19nor-D(3) (RO(4)) was tested vs. calcitriol in parathyroidectomized rats. In a second set of experiments, the effects of RO(2), RO(4) and calcitriol were studied in 5/6 nephrectomized rats with secondary hyperparathyroidism.

RESULTS

In parathyroidectomized rats, all analogs (250 pmol/day) led calcemia to rise after 7 days. In uremic rats, all treatments reduced PTH levels. RO(4) revealed toxicity. RO(2) was as effective as calcitriol in suppressing PTH in a dose dependent manner. Mean plasma ionized calcium did not change from baseline to day 14 and day 28 on RO(2) (250 or 500 pmol/day) whereas it increased significantly on RO(2) (1,000 pmol/day) and calcitriol (125 or 250 pmol/day). Increasing the dose of calcitriol led Ca x P to rise more dramatically than increasing the dose of RO(2), which appears to have a wider therapeutic window than calcitriol.

CONCLUSION

1,25-(OH)(2)-16ene-23yne-D(3) (RO(2)) may represent a novel candidate for the treatment of renal osteodystrophy in humans.

摘要

目的

比较维生素D类似物与骨化三醇对血清钙、磷和甲状旁腺激素（PTH）水平的影响。一种比骨化三醇更好的化合物在使PTH水平同等降低的情况下，应使钙磷乘积的升高幅度小于骨化三醇。

方法

在甲状旁腺切除的大鼠中测试了4种维生素D类似物1,25-(OH)(2)-16烯-D(3)（RO(1)）、1,25-(OH)(2)-16烯-23炔-D(3)（RO(2)）、1,25-(OH)(2)-26,27-六氟-16烯-23炔-D(3)（RO(3)）和1,25-(OH)(2)-16烯-23炔-26,27-六氟-19去甲-D(3)（RO(4)）与骨化三醇的生物活性。在第二组实验中，研究了RO(2)、RO(4)和骨化三醇对5/6肾切除继发甲状旁腺功能亢进大鼠的影响。

结果

在甲状旁腺切除的大鼠中，所有类似物（250 pmol/天）在7天后均导致血钙升高。在尿毒症大鼠中，所有治疗均降低了PTH水平。RO(4)显示出毒性。RO(2)在抑制PTH方面与骨化三醇一样有效，呈剂量依赖性。在RO(2)（250或500 pmol/天）治疗下，从基线到第14天和第28天，平均血浆离子钙没有变化，而在RO(2)（1000 pmol/天）和骨化三醇（125或250 pmol/天）治疗下显著升高。增加骨化三醇的剂量比增加RO(2)的剂量导致钙磷乘积升高得更显著，这表明RO(2)的治疗窗比骨化三醇更宽。