Description
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)
2D
3 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.
