Effect of Dietary Calcium, Phosphate and Vitamin D Deprivation on the Pharmacokinetics of 1,25-Dihydroxyvitamin D₃ in the Rat

Summary

The in vivo regulation of circulating 1,25(OH)₂D₃ concentrations by vitamin D status and by dietary calcium and phosphate deficiency was studied. Adult rats were cannulated in the jugular vein and the clearance of physiological doses of 1,25(OH)₂D₃ monitored. In vitamin D-replete rats we investigated the effects of dietary calcium and phosphate deficiency on the elimination half life of 1,25(OH)₂D₃ The results showed no effect of dietary phosphate deficiency on the elimination half life of 1,25(OH)₂D₃. Dietary calcium deficiency resulted in a small increase of the 1,25(OH)₂D₃ elimination half life (P=0.04) (normal diet: 16.3±1.8 hrs, n=6; - Ca diet: 18.6±1.1 hrs, n=5; - P diet: 16.0±1.4 hrs, n=6; mean±SD). The experiments with the vitamin D deficient rats showed a marked increase in the elimination half life of 1,25(OH)2D₃ (36.4±6.8 hrs, n=7), when compared to the rats on the normal diet (P=0.001). From the experiments in the vitamin D replete rats one can infer that regulation of circulating 1,25(OH)₂D₃ concentrations by dietary calcium or phosphate takes place at the production site and not by changes in elimination rate. However, vitamin D status appears to regulate circulating 1,25(OH)₂D₃ concentrations also through an effect on the elimination rate.

Key-Words

1,25(OH)₂D₃ - Pharmacokinetics - Phosphate - Calcium - Rat