Pharmaeokinetics and Pharmacodynamics of 1,25-Dihydroxyvitamin D3in the Chick

Abstract

To relate the disposition kinetics of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] to its function, we injected a physiological dose of radiolabeled 1,25-(OH)2D3 (84.6 pmol) into the wing veins of vitamin D-deficient chicks. The concentration of calcium-binding protein in duodenal mucosal cytosol, the concentration of 1,25-(OH)2D3 in plasma and duodenal mucosa, and the total radioactivity in bone, kidney, liver, muscle, pancreas, spleen, plasma, and duodenal mucosa were determined in individual chicks from 1–72 h later. The uptake of 1,25-(OH)2D3 by the duodenal mucosa occurred quickly, reaching a peak concentration of 6.2 pmol/g wet wt at 3 h. This was followed by a rapid disappearance, the kinetics of which paralleled the terminal phase of plasma 1,25-(OH)2D3 disappearance. Intact 1,25-(OH)2D3 accounted for more than 75% of the total radioactivity in the duodenal mucosa for at least 36 h, but fell to 30% of the total radioactivity in plasma by 8 h. An unidentified metabolite which cochromatographed with 1,24...