The pharmacokinetic differences between 10- and 15-µg daily vitamin D doses.

ABSTRACT

AIMS: The reference nutrient intake for vitamin D in people aged ≥4 years is 10 µg/day (400 IU/day) in the UK, but the recommended daily allowance is 15 µg/day (600 IU/day) for people aged 1-70 years in the USA. Here, we aim to compare the 25-hydroxyvitamin D (25(OH)D) serum concentration profiles between the 2 doses. METHODS: With world-wide trial data of adults aged ≥18 years, 45-93 kg, we constructed a minimal physiologically based pharmacokinetics model of serum concentrations of vitamin D and 25(OH)D using nonlinear mixed effects modelling. We used this model to forecast the mean, 2.5th and 97.5th percentiles for serum 25(OH)D concentrations in British adults aged ≥16 years. RESULTS: Our final model used bodyweight to adjust volume of each compartment and maximum clearance of 25(OH)D. No other covariate was identified. The model accurately predicted independent data from trials of a broad range of dosing regimens. We simulated British adults and showed that circulating 25(OH)D concentrations in 95% of people taking 10 µg/day for a year is predicted to reach 50 nmol/L in 32 weeks, while 97.5% of those on 15 µg/day were predicted to attain this threshold within 28 weeks. CONCLUSION: Both doses are efficacious in >95% of the British population. The daily dose of 15 µg can help 97.5% of the British adults achieve 50 nmol/L serum 25(OH)D and reach the 25 nmol/L threshold in 4 weeks.