PubMed · 14802738
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J BOURRILLON. 1950. [Hypervitaminosis D2].. https://pubmed.ncbi.nlm.nih.gov/14802738/
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OBJECTIVE: To review the pharmacology, pharmacokinetics, effectiveness, safety, and therapeutic considerations related to the use of doxercalciferol in the treatment of secondary hyperparathyroidism. DATA SOURCES: A MEDLINE search (1966-June 2006) was conducted using the key words vitamin D, ergocalciferols, and secondary hyperparathyroidism. Text word searches were also performed for the terms 1-alpha-hydroxy-vitamin D(2), 1-alpha-hydroxyergocalciferol, Hectorol, and doxercalciferol. Searches were limited to studies published in English and conducted in human subjects. STUDY SELECTION AND DATA EXTRACTION: All published clinical studies evaluating the safety and effectiveness of doxercalciferol in secondary hyperparathyroidism were reviewed, and anecdotal patient reports were also evaluated. Selected clinical studies involving the use of calcitriol and/or paricalcitol in the treatment of secondary hyperparathyroidism were also included. DATA SYNTHESIS: Doxercalciferol effectively reduces parathyroid hormone levels in patients with chronic kidney disease (CKD). Both oral and intravenous administration can significantly increase serum calcium and/or phosphorus levels as evidenced by placebo-controlled clinical trials. This agent has not been studied comparatively with calcitriol or paricalcitol to assess relative safety. CONCLUSIONS: Doxercalciferol is approved for and effective in the treatment of secondary hyperparathyroidism related to CKD, both before and during dialysis, but has not demonstrated a lower incidence of hypercalcemia and/or hyperphosphatemia in relation to other vitamin D therapies. The drug is available in both oral and intravenous dosage forms. Doxercalciferol should be maintained as a formulary alternative for patients unresponsive to or intolerant of other vitamin D therapies, but comparative randomized studies are needed to differentiate its place in therapy.
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Synthesis of a 1 alpha,25-dihydroxyvitamin D2 analog (3), in which the double bond in the side-chain is replaced by an amide group, is described. Condensation of a carboxylic acid (8) with an amine (6) gave an amide (9), which in turn led to 3 via several steps. The analog (3) could not bind to the chick cytosol vitamin D receptor, which indicated the importance of the hydrophobic interaction of the C(22)-C(23) double bond in 1 alpha,25-dihydroxyvitamin D2 (2) with the vitamin D receptor.