Metabolism of 1 alpha-hydroxyvitamin D2 to activated dihydroxyvitamin D 2 metabolites decreases endogenous 1 alpha, 25-dihydroxyvitamin D 3 in rats and monkeys

Endocrinology. 1995 Nov;136(11):4749-53. doi: 10.1210/endo.136.11.7588202.


The vitamin D analog 1 alpha-hydroxyvitamin D2 (1 alpha-OHD2) is under development for the treatment of secondary hyperparathyroidism and metabolic bone disease. This analog is metabolized in vivo to the natural active dihydroxylated metabolite of vitamin D2, 1 alpha,25-dihydroxyvitamin D2 [1 alpha,25-(OH)2D2]. To study the metabolism of this analog, an assay involving HPLC separation and purification of metabolites followed by RRA with the vitamin D receptor was developed to quantitate the active metabolites of the analog and the endogenous active metabolite of vitamin D3, 1 alpha,25-(OH)2D3, from the same blood sample. This assay was used to determine blood levels of active dihydroxylated vitamin D compounds in rats and monkeys treated with oral 1 alpha-OHD2. As the circulating 1 alpha,25-(OH)2D2 level increased dose dependently in these rats and monkeys, a concomitant decrease in the endogenous 1 alpha,25-(OH)2D3 was observed. In rats orally administered more than 2.5 micrograms 1 alpha-OHD2/, a second active metabolite of 1 alpha-OHD2, 1 alpha,24-(OH)2D2, was detected in concentrations similar to those of 1 alpha,25-(OH)2D2. These results indicate that the regulatory control of endogenous vitamin D metabolism as well as analog metabolism must be considered when assessing the therapeutic potential of a vitamin D analog.

MeSH terms

  • Animals
  • Calcitriol / blood
  • Calcitriol / metabolism*
  • Calcium / blood
  • Calcium / urine
  • Chromatography, High Pressure Liquid
  • Ergocalciferols / blood
  • Ergocalciferols / metabolism*
  • Female
  • Macaca fascicularis
  • Radioligand Assay / statistics & numerical data
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcitriol / metabolism
  • Sensitivity and Specificity


  • Ergocalciferols
  • Receptors, Calcitriol
  • 1 alpha-hydroxyergocalciferol
  • 1,25-dihydroxyergocalciferol
  • Calcitriol
  • Calcium