Pharmacological action and clinical effects of falecalcitriol, a highly potent derivative of active vitamin D3

Abstract

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.