Falecalcitriol, previously known as flocalcitrol, was launched by several codevelopers in Japan for the treatment of secondary
hyperthyroidism (SHPT). This hexafluorinated analog of 1α,25-dihydroxyvitamin D3
(calcitriol), the hormonally active form of vitamin D3, can be obtained by several different
synthetic routes from a conveniently protected cholestenol, a key step being an aldol
reaction with hexafluoroacetone. Falecalcitriol is several times more active than
1,25(OH)2D3 in regulating the proliferation of parathyroid cells and parathyroid hormone
(PTH) synthesis that are believed to be mediated through binding to VDR, a nuclear
receptor for vitamin D; furthermore, it was proposed that a bioactive 23S-hydroxylated
metabolite, resistant to further metabolism, contributes to the retention of an active
compound for longer in cells and so, to significantly lengthen the duration of action. In a
comparative clinical study conducted in hemodialysis patients with moderate to severe
SHPT, falecalcitriol was found to be more active than alfacalcidol in suppressing
parathyroid hormone without triggering hypercalcemia.
