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

Abstract: 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.