Pharmacokinetics of a single oral dose of vitamin D3 (70,000 IU) in pregnant and non-pregnant women

Abstract

Background: Improvements in antenatal vitamin D status may have maternal-infant health benefits. To inform the design of prenatal vitamin D3 trials, we conducted a pharmacokinetic study of single-dose vitamin D3 supplementation in women of reproductive age.

Methods: A single oral vitamin D3 dose (70,000 IU) was administered to 34 non-pregnant and 27 pregnant women (27 to 30 weeks gestation) enrolled in Dhaka, Bangladesh (23°N). The primary pharmacokinetic outcome measure was the change in serum 25-hydroxyvitamin D concentration over time, estimated using model-independent pharmacokinetic parameters.

Results: Baseline mean serum 25-hydroxyvitamin D concentration was 54 nmol/L (95% CI 47, 62) in non-pregnant participants and 39 nmol/L (95% CI 34, 45) in pregnant women. Mean peak rise in serum 25-hydroxyvitamin D concentration above baseline was similar in non-pregnant and pregnant women (28 nmol/L and 32 nmol/L, respectively). However, the rate of rise was slightly slower in pregnant women (i.e., lower 25-hydroxyvitamin D on day 2 and higher 25-hydroxyvitamin D on day 21 versus non-pregnant participants). Overall, average 25-hydroxyvitamin D concentration was 19 nmol/L above baseline during the first month. Supplementation did not induce hypercalcemia, and there were no supplement-related adverse events.

Conclusions: The response to a single 70,000 IU dose of vitamin D3 was similar in pregnant and non-pregnant women in Dhaka and consistent with previous studies in non-pregnant adults. These preliminary data support the further investigation of antenatal vitamin D3 regimens involving doses of ≤70,000 IU in regions where maternal-infant vitamin D deficiency is common.

Trial registration: ClinicalTrials.gov NCT00938600.

Figure 1

Flow diagram of participant screening, exclusions, and enrollment.

Figure 2

Blood and urine specimen collection schedules. Participants in “single-dose only” groups were randomized to one of two schedules (A or B) of specimen collection over a period 70 days. Participants in the “weekly dose” groups were similarly randomized to one of two schedules (C or D); however, the analysis of single-dose pharmacokinetics only included those specimens collected up to and including day 7, preceding administration of the 2nd vitamin D dose.

Figure 3

Serum [25(OH)D] in non-pregnant (A) and pregnant (B) participants following administration of 70,000 IU vitamin D3 at day 0. Predicted mean [25(OH)D] and 95% confidence intervals were estimated in a random-intercept regression model of ln[25(OH)D] as a function of time.

Figure 4

Albumin-adjusted serum calcium concentration ([Ca]) in non-pregnant (A) and pregnant participants (B) following administration of vitamin D3 70,000 IU at day 0. Dashed horizontal lines represent upper and lower bounds of the reference range. Predicted means and 95% confidence intervals were estimated in a linear regression model using GEE.

Figure 5

Calcium:creatinine ratios (Ca:Cr) in spot urine specimens from non-pregnant (A) and pregnant participants (B) following administration of vitamin D3 70,000 IU at day 0. Predicted means and 95% confidence intervals were estimated in a linear regression model using GEE, in which log-transformed Ca:Cr was modeled as a function of time.

Figure 6

Serum and urine biochemistry in a pregnant participant with two episodes of urine ca:cr > 1.0 mmol/mmol and one episode of serum albumin-adjusted [Ca] > 2.60 mmol/L. Vertical line indicates timing of delivery at 39 weeks gestation.