| Abstrakt: |
AbstractObjectives: 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- D3 (RO1), 1,25-(OH)2-16ene-23yne-D3 (RO2), 1,25-(OH)2-26,27-hexafluoro-16ene-23yne-D3 (RO3) and 1,25-(OH)2-16ene-23yne-26,27-hexafluoro-19nor-D3 (RO4) was tested vs. calcitriol in parathyroidectomized rats. In a second set of experiments, the effects of RO2, RO4 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. RO4 revealed toxicity. RO2 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 RO2 (250 or 500 pmol/day) whereas it increased significantly on RO2 (1,000 pmol/day) and calcitriol (125 or 250 pmol/day). Increasing the dose of calcitriol led Ca × P to rise more dramatically than increasing the dose of RO2, which appears to have a wider therapeutic window than calcitriol. Conclusion: 1,25-(OH)2-16ene-23yne-D3 (RO2) may represent a novel candidate for the treatment of renal osteodystrophy in humans.Copyright © 2004 S. Karger AG, Basel |
