A New Look at the Most Successful Prodrugs for Active Vitamin D (D Hormone): Alfacalcidol and Doxercalciferol

Alfacalcidol (1α-hydroxyvitamin D3) has been widely used since 1981 as a prodrug for calcitriol (1α,25-dihydroxyvitamin D3) in the treatment of hypocalcemia, chronic renal failure, hypoparathyroidism and osteoporosis. More recently, doxercalciferol (1α-hydroxyvitamin D2) has been used since 1999 as a prodrug for 1α,25-dihydroxyvitamin D2 for the treatment of secondary hyperparathyroidism. Currently, six forms of vitamin D are known. They range from vitamin D2 to vitamin D7 and are distinguished by their differing side chains. Only vitamin D2 and vitamin D3 have been found to be biologically active based on the elucidation of activation pathways. Alfacalcidol and osteoporosis/doxercalciferol and secondary hyperparathyroidism are discussed, with a new look at old compounds including their practical syntheses