A novel synthetic vitamin D3 analogue, 2-beta-(3-hydroxypropoxy)-calcitriol (ED-71): its biological activities and pharmacological effects on calcium metabolism.
A novel vitamin D3 analogue, [2 beta-(3-hydroxypropoxy)-calcitriol: ED-71] showed a similar Ca-regulating activity as calcitriol in the in vivo and in vitro Ca mobilization test and ex vivo intestinal Ca absorption assay using vitamin D-deficient rats. The differentiation-inducing activity of ED-71 in mouse myeloid leukemia cell line (WEHI-3 cell) was slightly less than that of calcitriol. ED-71 distributes predominantly in plasma as an intact form and its half-life plasma was twice as long as that of calcitriol. Further study revealed that the higher binding potency of ED-71 to plasma-specific vitamin D-binding protein (DBP) compared with that of calcitriol accounts for its stability in the blood circulation. The pharmacological effect of ED-71 for the animal models with osteoporosis seemed to be better than that calcitriol. These results suggest that ED-71 should become a valuable therapeutic long-acting drug for patients with osteoporosis.
Okano
T
T
Department of Hygienic Sciences, Kobe Women's College of Pharmacy, Japan.
Tsugawa
N
N
Masuda
S
S
Takeuchi
A
A
Kobayashi
T
T
Nishii
Y
Y
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D008297:Male; D010024:Osteoporosis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014807:Vitamin D / Q000031:analogs & derivatives
D014807:Vitamin D; D002117:Calcitriol; C547512:eldecalcitol; D002118:Calcium