Pharmacokinetics of oral vitamin D3 and calcifediol

Abstract

Aim: Long-term pharmacokinetics after supplementation with vitamin D3 or calcifediol (the 25-hydroxyvitamin D3 metabolite) is notwell studied. Additionally, it is unclearwhether bolus doses of vitamin D3 or calcifediol lead to 25(OH)D3 plasma concentrations considered desirable for fracture prevention (30 ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D3 during different vitamin D3 and calcifediol supplementation regimens. Methods: In this seven-arm, randomized, double-blind, controlled parallel-group study, 35 healthy females aged 50–70years (5 per group) received 20μg calcifediol or vitaminD3 daily, 140μg calcifediol or vitaminD3 weekly, for 15 weeks, or a single bolus of either 140 μg calcifediol, or vitaminD3, or both. 25(OH)D3 plasma concentrations were quantified using LC–MS/MS in 14 clinical visits among all participants. Results: For daily (weekly) dosing, the area under the concentration–timecurve (AUC0–24h),which is themeasure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitamin D3. After 15 weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH)D3 concentrations N30 ng/mL (mean, 16.8 days), but only 70% in the vitamin D3 daily or weekly groups reached this concentration (mean, 68.4 days). A single dose of 140 μg calcifediol led to 117% higher 25(OH)D3 AUC0–96h values than 140μg vitamin D3,while the simultaneous intake of both did not further increase exposure. Conclusions: Calcifediol given daily, weekly, or as a single bolus is about 2–3 times more potent in increasing plasma 25(OH)D3 concentrations than vitamin D3. Plasma 25(OH)D3 concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol.