Model of Vitamin D and metabolites reaction to 5,000 IU daily – Sept 2022

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Physiologically Based Pharmacokinetic Modeling of Vitamin D 3 and Metabolites in Vitamin D-Insufficient Patients

Drug Metab Dispos. 2022 Sep;50(9):1161-1169 doi: 10.1124/dmd.121.000609
Colton W Sawyer 1 , Stacey M Tuey 2 , Raymond E West 3rd 2 , Thomas D Nolin 2 , Melanie S Joy 2

A physiologically based pharmacokinetic (PBPK) model of vitamin D3 and metabolites [25(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3] is presented. In this study, patients with 25(OH)D3 plasma concentrations below 30 ng/ml were studied after a single dose of 5000 I.U. (125 µg) cholecalciferol, provided with 5000 I.U. daily cholecalciferol supplementation until vitamin D replete [25(OH)D3 plasma concentrations above 30 ng/ml], and had serial plasma samples were collected at each phase for 14 days. Total concentrations of vitamin D3 and metabolites were measured by ultra-high performance liquid chromatography tandem mass spectrometry. A nine-compartment PBPK model was built using MATLAB to represent the triphasic study nature (insufficient, replenishing, and sufficient). The stimulatory and inhibitory effect of 1,25(OH)2D3 were incorporated by fold-changes in the primary metabolic enzymes CYP27B1 and CYP24A1, respectively. Incorporation of dynamic adipose partition coefficients for vitamin D3 and 25(OH)D3 and variable enzymatic reactions aided in model fitting. Measures of model predictions agreed well with data from metabolites, with 97%, 88%, and 98% of the data for 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3, respectively, within twofold of unity (fold error values between 0.5 and 2.0). Bootstrapping was performed and optimized parameters were reported with 95% confidence intervals. This PBPK model could be a useful tool for understanding the connections between vitamin D and its metabolites under a variety of clinical situations.
SIGNIFICANCE STATEMENT: This study developed a physiologically based pharmacokinetic (PBPK) model of vitamin D3 and metabolites for patients moving from an insufficient to a repleted state over a period of 16 weeks.
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VitaminDWiki is confused

They state that 5,000 IU was given until >30ng . but it seems that most started higher than 30ng
Do not know what the blue lines and red dots represent - cannot find a caption
The final PDF costing $35 for the next 12 months may eliminate the confusion

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