生物活性

• 描述Vitamin D3 receptor is a member of the nuclear hormone receptor superfamily of ligand-inducible transcription factors. It is the nuclear receptor for calcitriol which is the active form of vitamin D3 which mediates the action of this vitamin on cells. Vitamin D3 receptor enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Downstream targets of vitamin D3 receptor are principally involved in mineral metabolism and vitamin D3 receptor plays a central role in calcium homeostasis. Calcifediol, also known as calcidiol, is a prehormone that is produced in the liver by hydroxylation of vitamin D3. Calcifediol is further hydroxylated by CYP27B1 to form the active metabolite, calcitriol. Calcitriol is a vitamin D3 receptor (VDR) agonist. According to a report, neonatal rat cardiomyocytes were treated with the prehormone calcidiol in the presence of aldo (1 μM). Calcidiol induced VDR expression in the presence of aldo with EC50 at 7952 nM. Calcidiol also stimulated CYP24A1 with EC50 at 992 nM and suppressed NPPB expression with IC50 at 210 nM in the presence of 1 μM aldo. In another study, calcifediol was encapsulated in liposomes to enable aerosolisation, and tested for the ability to prevent pulmonary infection by Pseudomonas aeruginosa. Treatment of infected, human bronchial 16-HBE cells with liposomes containing 40 ng calcifediol resulted in a significant reduction in bacterial survival.In vivo, the active metabolite, calcitriol was injected at the dose of 50 ng daily for 3 days to SHR or WKY rats. Calcitriol increased total cell and brush border calbindin-D9K in both strains but had no effect on calmodulin in either strain.

• 动物研究
  剂量	Mice: 10 μg/kg[3] (p.o.) Rat: 4.5 μg/kg[3] (i.v./p.o.)
  给药途径	p.o., i.v.
  动物药代数据	Animal Mice[3] Dose 100 μg/kg Administration p.o. s.c. i.v. F 20.3% (p.o.) 92.3% (s.c.) Tmax 4 h (p.o.) 4 h (s.c.) 4 h (i.v.) Cmax 163 ± 12.9 ng/ml (p.o.) 510 ng/ml (s.c.) 589 ± 62.7 ng/ml (i.v.) AUC0→t 2090 ± 97.0 ng·h/ml (p.o.) 9510 ± 371 ng·h/ml (s.c.) 10300 ± 363 ng·h/ml (i.v.)