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Effects of 1.28 nmol/kg doxercalciferol [1 alpha(OH)D(2)], a synthetic vitamin D(2) analog that undergoes metabolic activation to 1 alpha,25-dihydroxyvitamin D(2), the naturally occurring, biologically active form of vitamin D(2), on rat transporters and enzymes were compared with those of 1 alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3), active form of vitamin D(3); 4.8 and 6.4 nmol/kg] given on alternate days intraperitoneally for 8 days. Changes were mostly confined to the intestine and kidney where the vitamin D receptor (VDR) was highly expressed: increased intestinal Cyp24 and Cyp3a1 messenger RNA (mRNA) and a modest elevation of apical sodium-dependent bile salt transporter (Asbt) and P-glycoprotein (P-gp) protein; increased renal VDR, Cyp24, Cyp3a9, Mdr1a, and Asbt mRNA, as well as Asbt and P-gp protein expression; and decreased renal PepT1 and Oat1 mRNA expression. In comparison, 1 alpha(OH)D(2) treatment exerted a greater effect than 1,25(OH)(2)D(3) on Cyp3a and Cyp24 mRNA. However, the farnesoid X receptor -related repressive effects on liver Cyp7a1 were absent because intestinal Asbt, FGF15 and portal bile acid concentrations were unchanged. Rats on the alternate day regimen showed milder changes and lessened signs of hypercalcemia and weight loss compared with rats receiving daily injections (similar or greater amounts of 0.64-2.56 nmol/kg daily x4) described in previous reports, showing that the protracted pretreatment regimen was associated with milder inductive and lesser toxic effects in vivo. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 1594-1604, 2011

1 alpha,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3), a natural ligand of the vitamin D receptor (VDR), was found to increase the rat ileal Asbt and bile acid absorption. The effects of VDR, whose expression is low in liver, on hepatic transporters and enzymes are Unknown Protein and mRNA levels of target genes in the small intestine, colon and liver after intraperitoneal closing of 1,25(OH)(2)D-3 (0-2.56 nmol/kg/day for 4 days) to the rat were determined by Western blotting and qPCR, respectively The 1,25(OH)(2)D-3 treatment increased total Cyp3a protein and Cyp3a1 mRNA expressions in the proximal small intestine, and the short heterodimer partner (SHP), the fibroblast growth factor,15 (FGF15), organic solute transporter (Ost alpha and Ost beta) mRNA and Asbt protein expressions in the ileum About 50% higher portal bile acid concentration (65.1 +/- 14.9 vs 419 +/- 7.8 mu M, p 50% reduction in the Cyp7a1 protein level (p