Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults

Abstract

25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18-23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life.

Fig. 1

Plasma appearance and disappearance over 48 h after an oral dose of 25-hydroxyvitamin D₂ (25(OH)D₂) in the absorption group. Values are means (n 6), with standard deviations represented by vertical bars, and the mean modelled plasma concentration represented by a dashed line (n 6).

Fig. 2

Plasma appearance and disappearance over 48 h after an oral dose of 25-hydroxyvitamin D₂ (25(OH)D₂) in six subjects (A–F) in the absorption group. ○, Observed plasma concentration of 25(OH)D₂; —, modelled plasma curve.

Fig. 3

Semi-logarithmic plot of plasma concentration between days 3 and 21 after an oral dose of 25-hydroxyvitamin D₂ (25(OH)D₂) in the half-life group (n 6). Values are means, with standard deviations represented by vertical bars, and the terminal slope (0·05 (sd 0·01)) calculated from day 6 onwards represented by a dashed line.

Fig. 4

Semi-logarithmic plot of plasma disappearance from days 3 to 21 after an oral dose of 25-hydroxyvitamin D₂ (25(OH)D₂) in six subjects (H–M) in the half-life group. ○, Observed plasma concentration of 25(OH)D₂; —, line of best fit between days 6 and 21.