Vitamin D kinetics in nonpregnant and pregnant women after a single oral dose of trideuterated vitamin D3

The plasma pool of the hormone 1,25-dihydroxyvitamin D (1,25(OH)(2)D) is increased throughout most of human pregnancy. Mechanisms behind this adaptation are unclear, in part due to limited data on vitamin D kinetics during pregnancy. Stable isotopes make it possible to study vitamin D kinetics in vulnerable study populations like pregnant women. We conducted a pilot study of vitamin D kinetics in nonpregnant and pregnant women. We evaluated a clinical protocol and developed analytical methods to assess the serum appearance and disappearance of trideuterated vitamin D-3 (d3-vitamin D-3) and trideuterated 25-hydroxyvitamin D-3 (d3-25(OH)D-3) after a single oral dose of 25 mu g of [6,19,19-H-2]-vitamin D-3 (d3-vitamin D-3). Blood was collected at baseline and 2, 4, 6, 24, 168, 264, and 456 hours post-dosing. We then described the serum kinetic profiles of d3-vitamin D-3 and d3-25(OH)D-3 in nonpregnant and pregnant women. Serum kinetic profiles of d3-vitamin D-3 and d3-25(OH)D-3 followed a time course in line with previous pharmacokinetic studies. There was marked variability between participants in the area under the concentration-time curve (AUC) of d3-25(OH)D-3 over the 20-day study period. This AUC of d3-25(OH)D-3 was positively correlated with the serum vitamin D binding protein (DBP) concentration, which was higher in pregnant compared with nonpregnant women. The mean serum half-life of 25(OH) D-3 was longer but not significantly different in pregnant women (18.8 days) compared with nonpregnant women (13.6 days). Our pilot study demonstrated that a single oral dose of 25 mu g of d3-vitamin D-3 can be used to study vitamin D kinetics. Serum DBP concentration is an important predictor of vitamin D kinetics, and more research is needed to fully understand the significance of elevated DBP concentration during pregnancy.