Abstract | UNLABELLED: INTRODUCTION: MATERIALS AND METHODS: RESULTS:
Uremia produced a marked rise in plasma PTH, but treatment every other day for 2 wk with either 1,25(OH)(2)D(3) (4 ng) or 2MbisP (250, 750, 1500, or 3000 ng) suppressed this increase by >50%. The suppression by 1,25(OH)(2)D(3), however, was accompanied by increases in ionized calcium, phosphorus, and the calcium x phosphorus product, whereas these three parameters were unchanged by 2MbisP. The binding affinity of 2MbisP was 10-20 times less for the vitamin D receptor and 1000 times less for the serum vitamin D-binding protein compared with 1,25(OH)(2)D(3). Also, 2MbisP was cleared more rapidly from the circulation (t1/2 = 10 min) than 1,25-(OH)(2)D(3) (t1/2=7-9 h). In parathyroidectomized rats fed calcium-or phosphorus-deficient diets, daily injections of 2MbisP (1500 or 3000 ng), unlike 1,25(OH)(2)D(3) (50 ng), had no effect on calcium or phosphorus mobilization from bone. CONCLUSIONS:
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Authors | Eduardo Slatopolsky, Jane L Finch, Alex J Brown, Cynthia S Ritter, Masahide Mizobuchi, Lori A Plum, Margaret Clagett-Dame, Rafal R Sicinski, Hector F DeLuca |
Journal | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
(J Bone Miner Res)
Vol. 22
Issue 5
Pg. 686-94
(May 2007)
ISSN: 0884-0431 [Print] United States |
PMID | 17444814
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dihydroxycholecalciferols
- Receptors, Calcitriol
- Vitamin D-Binding Protein
- Vitamins
- Phosphorus
- Calcitriol
- 2-methylene-19-nor-(20S)-1 alpha-hydroxy-bishomopregnacalciferol
- Calcium
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Topics |
- Animals
- Calcinosis
(chemically induced, metabolism, pathology)
- Calcitriol
(adverse effects, analogs & derivatives, pharmacokinetics)
- Calcium
(metabolism)
- Chronic Disease
- Dihydroxycholecalciferols
(pharmacology)
- Dose-Response Relationship, Drug
- Drug Evaluation, Preclinical
- Female
- Humans
- Hyperparathyroidism, Secondary
(drug therapy, etiology, metabolism, pathology)
- Phosphorus
(metabolism)
- Protein Binding
(drug effects)
- Rats
- Rats, Sprague-Dawley
- Receptors, Calcitriol
(metabolism)
- Uremia
(complications, drug therapy, metabolism, pathology)
- Vascular Diseases
(chemically induced, metabolism, pathology)
- Vitamin D-Binding Protein
(metabolism)
- Vitamins
(adverse effects, pharmacokinetics)
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