Synthesis and metabolic clearance of 1,25-dihydroxyvitamin D as determinants of serum concentrations: a comparison of two methods.

We evaluated endogenous renal 1,25-dihydroxyvitamin D (1,25-OH)2D) synthesis by compartmental analysis of the plasma disappearance of injected [3H]1,25-dihydroxyvitamin D3 in 11 subjects with serum 1,25-(OH)2D concentrations varying from 9-154 pM (normal, 89 +/- 25 pM). Estimated renal synthesis ranged from 2-180 pmol/kg . day. Serum 1,25-(OH)2D concentrations in these subjects best fit a log function of renal synthesis: serum 1,25-(OH)2D, pM = -13 + 74 log renal 1,25-(OH)2D production, picomoles per kg/day (r = 0.91). We also evaluated serum 1,25-(OH)2D concentrations in 6 healthy subjects who had been given 0.6, 1.2, or 1.8 nmol calcitriol every 6 h during a period 6--12 days after hormone administration was begun. Steady serum 1,25-(OH)2D concentrations 2, 4, and 6 h after the last calcitriol dose were achieved in proportion to log dose: serum 1,25-(OH)2D, pM = -12 + 103 log 1,25-dihydroxyvitamin D3 dose, picomoles per kg/day (r = 0.94). Estimated 1,25-(OH)2D production rates using these two methods and assuming a normal serum 1,25-(OH)2D concentration of 89 pM range from 10--24 pmol/kg . day or, for a 70-kg subject, 0.6--1.7 nmol/day or 0.25--0.7 microgram/day. Metabolic clearance of 1,25-(OH)2D appears to be accelerated when production rates are increased.