title: Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis.
abstract: BACKGROUND
  We previously showed that a single high dose of oral (po) cholecalciferol (D₃) 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 (D₂) or D₃.
  
  
  METHODS
  This was a prospective intervention study.
  
  
  METHODS
  The study was conducted in an ambulatory care setting.
  
  
  METHODS
  Participants were 24 subjects with hypovitaminosis D.
  
  
  METHODS
  A single dose of 600,000 IU of po or im D₂ or D₃ was administered.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine and Medical Disciplines, Sapienza Rome University, 00161 Rome, Italy. cristianac@alice.it
authors.forename: Cristiana
authors.initials: C
authors.lastname: Cipriani
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Romagnoli
authors.forename: Jessica
authors.initials: J
authors.lastname: Pepe
authors.forename: Stefania
authors.initials: S
authors.lastname: Russo
authors.forename: Luciano
authors.initials: L
authors.lastname: Carlucci
authors.forename: Sara
authors.initials: S
authors.lastname: Piemonte
authors.forename: Luciano
authors.initials: L
authors.lastname: Nieddu
authors.forename: Donald J
authors.initials: DJ
authors.lastname: McMahon
authors.forename: Ravinder
authors.initials: R
authors.lastname: Singh
authors.forename: Salvatore
authors.initials: S
authors.lastname: Minisola
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000097:blood; D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D000284:Administration, Oral; D000368:Aged; D001682:Biological Availability; D001711:Biotransformation; D002112:Calcifediol / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004872:Ergocalciferols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D004872:Ergocalciferols; D002762:Cholecalciferol; D015652:25-Hydroxyvitamin D 2; D015650:24,25-Dihydroxyvitamin D 3; C028140:24,25-dihydroxyvitamin D2; D002112:Calcifediol