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Personalise vitamin D3 using physiologically based pharmacokinetic modelling.

Zhonghui Huang1, Tao You1

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This summary is machine-generated.

This study developed a physiologically-based pharmacokinetic model to accurately predict vitamin D levels. The model suggests the UK's 10 µg daily dose may be insufficient for achieving vitamin D sufficiency.

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Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Nutritional Biochemistry
  • Computational Biology

Background:

  • Vitamin D (25(OH)D3) plasma concentrations vary significantly between individuals.
  • Current recommended daily vitamin D doses may not be universally effective.

Purpose of the Study:

  • To develop an accurate physiologically-based pharmacokinetic (PBPK) model for vitamin D3 and its metabolite 25-hydroxyvitamin D3 (25(OH)D3).
  • To support personalized vitamin D3 dosage regimens.
  • To evaluate the efficacy of current UK public health advice on vitamin D supplementation.

Main Methods:

  • Collated vitamin D3 and 25(OH)D3 plasma pharmacokinetic data from clinical trials.
  • Developed and validated a PBPK model incorporating first-order vitamin D3 absorption and metabolism, and nonlinear 25(OH)D3 elimination.
  • Predicted plasma 25(OH)D3 concentrations under various dosing scenarios.

Main Results:

  • The PBPK model accurately predicted plasma 25(OH)D3 levels for repeated dosing up to 1250 μg/d and large single doses up to 50,000 μg.
  • Observed a negative correlation between baseline 25(OH)D3 levels and the increase in plasma 25(OH)D3 after repeated dosing.
  • Predicted that a 10 μg/d regimen may be insufficient for severely deficient individuals, potentially requiring over 200 days to reach sufficiency at 20 μg/d.

Conclusions:

  • The developed PBPK model accurately predicts vitamin D3 pharmacokinetics and can inform personalized supplementation protocols.
  • The current UK recommended 10 μg/d vitamin D3 dose is likely insufficient for achieving optimal plasma 25(OH)D3 levels (≥ 75 nmol/L) in many individuals.
  • Personalized vitamin D supplementation, guided by baseline 25(OH)D3 measurements and PBPK modeling, can improve treatment effectiveness for hypovitaminosis D.