A. Jetter, A. Egli, B. Dawson-Hughes
Feb 1, 2014
Citations
2
Influential Citations
103
Citations
Quality indicators
Journal
Bone
Abstract
AIM Long-term pharmacokinetics after supplementation with vitamin D3 or calcifediol (the 25-hydroxyvitamin D3 metabolite) are not well studied. Additionally, it is unclear whether bolus doses of vitamin D3 or calcifediol lead to 25(OH)D3 plasma concentrations considered desirable for fracture prevention (30ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D3 during different vitamin D3 and calcifediol supplementation regimens. METHODS In this seven-arm, randomised, 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 15weeks, or a single bolus of either 140μg 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-time curve (AUC0-24h), which is the measure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitaminD3. After 15weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH)D3 concentrations >30ng/mL (mean, 16.8days), but only 70% in the vitaminD3 daily or weekly groups reached this concentration (mean, 68.4days). A single dose of 140μg calcifediol led to 117% higher 25(OH)D3 AUC0-96h values than 140μg vitaminD3, 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 30ng/mL were reached more rapidly and reliably with calcifediol.