Acute Administration of 25-hydroxycholecalciferol in Man

Serum 25-hydroxyvitamin D responses to oral doses of 25-hydroxycholecalciferol were measured in healthy volunteers. Peak serum 25-hydroxyvitamin D levels occurred 4 to 8 hours after doses of 1.5, 5, and 10 mug per kg of body weight. The mean increments above baseline serum 25-hydroxyvitamin D concentrations at 4 hours were linear over this dose range. Following a single oral dose, serum 25-hydroxyvitamin D levels fell to 33% of their peak values after one week. The serum 25-hydroxyvitamin D responses measured by competitive protein-binding radioassay were similar to the serum 3H responses exhibited by three volunteers who received simultaneous oral doses of 3H 25-hydroxycholecalciferol and 14C-cholecalciferol. The appearance of 14C in plasma was slower and less marked compared with 3H, probably reflecting a more rapid plasma clearance of the 14C-cholecalciferol. The disappearance of 25-hydroxycholecalciferol from the circulation of two volunteers following acute intravenous delivery of 1.0 mg of 25-hydroxycholecalciferol was multiphasic over 10 days. 60% of the dose administered remained in the circulation 24 hours after the dose. When analyzed several days after single 10 mug/kg oral doses of 25-hydroxycholecalciferol to 4 volunteers, the mean rate of decline to total serum 25-hydroxycholecalciferol was slow (t 1/2 = 22 days). When baseline serum 25-hydroxyvitamin D levels were subtracted, however, the apparent serum half-life of administered 25-hydroxycholecalciferol was 12 days, similar to that reported after tracer doses of 3H-25-hydroxycholecalciferol. The rapid and predictable serum 25-hydroxyvitamin D increases following the oral administration of 25-hydroxycholecalciferol suggest its possible therapeutic advantages compared with vitamin D administration.