Statistical analysis was performed using the SAS System for Windows (SAS Institute, Cary, NC, USA). Statistical significance was determined by Tukey’s test in Section 2.2.1, and by Dunnett’s test in Section 2.2.2. A dose of 2 μg/kg calcitriol or 0.2 μg/kg eldecalcitol administered daily by oral gavage for 14 days significantly increased BIBW2992 serum calcium and urinary calcium excretion compared with vehicle administration in WT mice. However, neither eldecalcitol nor calcitriol affected serum or urinary calcium in the VDRKO mice (Fig. 1A and

B). Calcitriol and eldecalcitol significantly increased the expression of renal TRPV5 and calbindin-D28k mRNA and the expression of intestinal TRPV6 and calbindin-D9k mRNA in the WT mice. On the other hand, the expression of these genes in the VDRKO mice was not altered by the treatment (Fig. 1C–F). These results indicate that the calcemic actions of calcitriol and eldecalcitol are mediated by VDR. Eldecalcitol (0.025, 0.05, 0.1, 0.25, and 0.5 μg/kg) or calcitriol (0.25, 0.5, 1, 2.5, and 5 μg/kg) administered daily by oral gavage for 14 days dose-dependently increased the blood concentration of each compound. The blood concentration of each compound correlated well with the administered dosage (eldecalcitol: y (pmol/L) = 29,834x (μg/kg) + 646.3, R2 = 0.996; calcitriol: y (pmol/L) = 681.81x (μg/kg) + 402.1, R2 = 0.971) ( Fig. 2A and B). This result indicates that in order to

reach the same concentration in the blood, the amount of eldecalcitol Etomidate required is approximately 1/40 that of calcitriol. In the eldecalcitol-treated rats, serum concentration of calcitriol dose-dependently decreased and selleck inhibitor fell to below the limit of detection at 0.1 μg/kg (

Fig. 2C). Treatment with eldecalcitol and calcitriol significantly reduced renal CYP27B1 gene expression and dose-dependently increased renal CYP24A1 gene expression ( Fig. 2D and E). These results suggest that the administration of eldecalcitol and calcitriol reduces endogenous production of calcitriol and stimulates degradation of calcitriol in the kidneys. Blood concentrations of eldecalcitol and calcitriol correlated with urinary phosphorus excretion. Serum phosphorus slightly decreased along with the increase in eldecalcitol concentration in blood, whereas calcitriol concentration did not alter serum phosphorus (Fig. 3A and B). Serum calcium was significantly elevated at higher blood concentrations of eldecalcitol (≥7520 pmol/L) and calcitriol (≥1170 pmol/L) (Fig. 3C). Urinary calcium excretion correlated with blood concentrations of calcitriol and eldecalcitol (Fig. 3D). Serum FGF-23 increased at 15,800 pmol/L of eldecalcitol and at ≥2480 pmol/L of calcitriol in blood (Fig. 3E). High concentrations of eldecalcitol in the blood (≥7520 pmol/L) suppressed plasma PTH concentration, whereas plasma PTH concentration was reduced from low blood calcitriol concentrations (≥590 pmol/L) (Fig. 3F).