Long-Term Bioavailability After a Single Oral or Intramuscular Administration of 600,000 IU of Ergocalciferol or Cholecalciferol: Implications for Treatment and Prophylaxis

Context: We previously showed that a single high dose of oral (po) cholecalciferol (D-3) sharply increases serum 25-hydroxyvitamin D [25(OH)D]. Objective: We evaluated the long-term bioavailability and metabolism of a single po or intramuscular (im) high dose of ergocalciferol (D-2) or D-3. Design: This was a prospective intervention study. Setting: The study was conducted in an ambulatory care setting. Patients: Participants were 24 subjects with hypovitaminosis D. Interventions: A single dose of 600,000 IU of po or im D-2 or D-3 was administered. Main Outcome Measures: Serum 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured at baseline and at days 30, 60, 90, and 120 by RIA. Serum 1,25(OH)(2)D-2, 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], 24,25-hydroxyvitamin D-2 [24,25(OH)D-2], and 24,25-hydroxyvitamin D-3 [24,25(OH)D-3] were measured by liquid chromatography-tandem mass spectrometry in a subgroup of patients receiving the po formulations. Results: The areas under the curve of 25(OH)D after D-3 were significantly higher than those after D-2 (P < .0001). Serum 25(OH)D basal difference significantly increased at day 30 with po D-2 and D-3 (P < .01 and P < .0001) and up to day 90 with po D-3 (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)(2)D at day 30 (P < .05) and up to day 120 (P < .001) and an increase in 1,25(OH)(2)D-2 at day 30 (P < .01) and up to day 120 (P < .01) after po D-2. Oral D-2 and D-3 produced increases in 24,25(OH)D-2 and 24,25(OH)D-3, respectively, at day 30 (P < .001). Conclusions: A po dose of 600,000 IU of D-2 or D-3 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)(2)D may not recognize 1,25(OH)(2)D-2.