Vitamin D kinetics in vivo: effect of 1,25-dihydroxyvitamin D administration

Administration of 1,25-dihydroxyvitamin D [1,25(OH)2D] can increase the metabolic clearance rate (MCR) of 25-hydroxyvitamin D [25(OH)D]. To determine whether administration of 1,25(OH)2D can also influence the metabolic clearance rates (MCR) of 1,25(OH)2D and 24,25-dihydroxyvitamin D 24,25(OH)2D, we measured metabolic clearance of 1,25(OH)2D, 24,25(OH)2D, and 25(OH)D in rats in which the serum concentration of 1,25(OH)2D was increased by continuous infusion. Infusion of 1,25(OH)2D (12 days at 75 pmol/day) increased serum 1,25(OH)2D from 128 +/- 11 to 244 +/- 14 pg/ml (P less than 0.005) and increased MCR from 169 +/- 13 to 210 +/- 9 microliters.min-1.kg-1 or 24% (P less than 0.025). Increasing serum 1,25(OH)2D to 330-360 pg/ml increased MCR 72%. Infusion of 1,25(OH)2D decreased serum 24,25(OH)2D from 3.5 +/- 0.5 to 2.4 +/- 0.3 ng/ml (P less than 0.05), increased MCR from 25 +/- 2 to 48 +/- 6 microliters.min-1.kg-1 (P less than 0.0025), and increased the production rate (PR) from 70 +/- 11 to 124 +/- 26 pg.min-1.kg-1 (P less than 0.05). Infusion of 1,25(OH)2D decreased serum 25(OH)D from 13.0 +/- 0.5 to 8.0 +/- 0.5 ng/ml (P less than 0.005) and increased MCR from 45 +/- 1 to 75 +/- 7 microliters.min-1.kg-1 (P less than 0.001) but had no effect on PR. The data indicate that increasing serum 1,25(OH)2D by chronic administration can increase the MCR of 1,25(OH)2D and suggest that 1,25(OH)2D can feedback regulate its serum concentration by regulating its MCR. The data also suggest that 1,25(OH)2D administration can increase the MCRs of 24,25(OH)2D and 25(OH)D.