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J Clin Endocrinol Metab. 2013 Jul;98(7):2709-15. doi: 10.1210/jc.2013-1586. Epub 2013 Jun 13.

Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis.

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  • 1Department of Internal Medicine and Medical Disciplines, Sapienza Rome University, 00161 Rome, Italy.



We previously showed that a single high dose of oral (po) cholecalciferol (D₃) sharply increases serum 25-hydroxyvitamin D [25(OH)D].


We evaluated the long-term bioavailability and metabolism of a single po or intramuscular (im) high dose of ergocalciferol (D₂) or D₃.


This was a prospective intervention study.


The study was conducted in an ambulatory care setting.


Participants were 24 subjects with hypovitaminosis D.


A single dose of 600,000 IU of po or im D₂ or D₃ was administered.


Serum 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)₂D] were measured at baseline and at days 30, 60, 90, and 120 by RIA. Serum 1,25(OH)₂D₂, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], 24,25-hydroxyvitamin D₂ [24,25(OH)D₂], and 24,25-hydroxyvitamin D₃ [24,25(OH)D₃] were measured by liquid chromatography-tandem mass spectrometry in a subgroup of patients receiving the po formulations.


The areas under the curve of 25(OH)D after D₃ were significantly higher than those after D₂ (P < .0001). Serum 25(OH)D basal difference significantly increased at day 30 with po D₂ and D₃ (P < .01 and P < .0001) and up to day 90 with po D₃ (P < .01). The im formulations produced a slow increased, and values peaked at day 120 relative to the other time points (P < .0001). We found a decrease in 1,25(OH)₂D at day 30 (P < .05) and up to day 120 (P < .001) and an increase in 1,25(OH)₂D₂ at day 30 (P < .01) and up to day 120 (P < .01) after po D₂. Oral D₂ and D₃ produced increases in 24,25(OH)D₂ and 24,25(OH)D₃, respectively, at day 30 (P < .001).


A po dose of 600,000 IU of D₂ or D₃ is initially more effective in increasing serum 25(OH)D than the equivalent im dose and is rapidly metabolized. Our RIA assay for 1,25(OH)₂D may not recognize 1,25(OH)₂D₂.

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