Much effort has been made to create highly potentiated active
vitamin D for better clinical applications and
falecalcitriol was successfully synthesized as one of such candidates with highly potent and long-lasting effects. Its chemical structure has a
calcitriol side chain modification in which both methyls at positions C-26 and
C-27 are substituted by tri-fluoromethyls. The mechanism for its strong and long-lasting effects is probably due to altered side chain metabolism and decreased inactivation. Although C-24 position hydroxylation catalyzed by Cyp24 inactivates
calcitriol, falecarcitriol is metabolized to C-23S hydroxylated metabolite by the same
enzyme Cyp24 and this metabolite still has strong activity. Stronger action of
falecalcitriol has been shown in target organs or cells of active
vitamin D such as bone, parathyroid cells, and keratinocytes, when compared with
calcitriol, the endogenous active form of
vitamin D. Daily
oral administration of
falecalcitriol at doses lower than those required for
calcitriol has been shown to have clinical effects for the treatment of diseases such as
hyperparathyroidism due to
chronic renal failure (2 degrees HPT),
rickets,
osteomalacia and
hypoparathyroidism. The comparative study with
alfacalcidol showed its specific action on
parathyroid hormone suppression and better improvement of bone metabolism markers in 2 degrees HPT patients.