SynthesisJournal of pharmacokinetics and pharmacodynamics2016
Model-based meta-analysis for development of a population-pharmacokinetic (PPK) model for Vitamin D3 and its 25OHD3 metabolite using both individual and arm-level data.
Synthesis in Journal of pharmacokinetics and pharmacodynamics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Applications of Model-Based Meta-Analysis in Drug Development.Pharmaceutical research · 2022Pooled it
- Longitudinal model-based meta-analysis for survival probabilities in patients with castration-resistant prostate cancer.European journal of clinical pharmacology · 2020Pooled it
- Model-based meta-analysis for comparing Vitamin D2 and D3 parent-metabolite pharmacokinetics.Journal of pharmacokinetics and pharmacodynamics · 2017Pooled it
- Pharmacokinetics of Oral Vitamin D in Children with Obesity and Asthma.Clinical pharmacokinetics · 2023Trial
- Serum Vitamin D: Correlates of Baseline Concentration and Response to Supplementation in VITAL-DKD.The Journal of clinical endocrinology and metabolism · 2022Trial
- Pharmacokinetic modeling of prenatal vitamin D exposure and the impact on offspring asthma and pulmonary function.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Population Pharmacokinetic Model of Vitamin DInternational journal of molecular sciences · 2024Article
- Vitamin D beyond the blood: Tissue distribution of vitamin D metabolites after supplementation.Life sciences · 2024Review
- Novel Approach for the Approximation of Vitamin DPharmaceutics · 2023Article
- Physiologically Based Pharmacokinetic Modeling of Vitamin DDrug metabolism and disposition: the biological fate of chemicals · 2022Article
- Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease.British journal of clinical pharmacology · 2022Article
- Personalise vitamin DCPT: pharmacometrics & systems pharmacology · 2021Article
- Vitamin D Metabolism and Guidelines for Vitamin D Supplementation.The Clinical biochemist. Reviews · 2020Review
- Data Digitizing: Accurate and Precise Data Extraction for Quantitative Systems Pharmacology and Physiologically-Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2020Review
- Article
- Concerning the vitamin D reference range: pre-analytical and analytical variability of vitamin D measurement.Biochemia medica · 2017Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical studies investigating relationships between D3 and 25OHD3 vary in dosing regimen, assays, demographics, and control of exogenous D3. This leads to uncertain and conflicting exposure-related associations with D3 and 25OHD3. To elucidate this parent-metabolite system, a PPK model was developed to predict mean D3 and 25OHD3 exposure from varied doses and administration routes. Sources of exposure variability related to metabolite baseline, weight, and assay type were explored. Specific search criteria were used in PUBMED to identify public source PK data pertaining to D3 and 25OHD3 in healthy or osteoporotic populations. Overall 57 studies representing 5395 individuals were selected, including 25 individual-level profiles and treatment-arm data. IV, oral, single and multiple dose data were used, with D3 and 25OHD3 dosing. A nonlinear mixed effects model was developed to simultaneously model PK dispositions of D3 and 25OHD3 (NONMEM v7.2), which were described by 2-compartment models with nonlinear and linear clearances, respectively. Proportional and additive assay variances were included on the 25OHD3 prediction. Unit-level random effects were weighted by treatment-arm size. D3 model estimates, relative to bioavailability were: maximum rate of metabolism ([Formula: see text], 1.62 nmol/h), Michaelis-Menten constant ([Formula: see text], 6.39 nmol/L), central volume of distribution ([Formula: see text], 15.5 L), intercompartmental clearance ([Formula: see text], 0.185 L/h), peripheral volume of distribution ([Formula: see text], 2333 L/h), and baseline concentration ([Formula: see text], 3.75 nmol/L). For 25OHD3 ([Formula: see text] = metabolite): [Formula: see text] = 0.0153 L/h, [Formula: see text] = 4.35 L, [Formula: see text] = 6.87 L, [Formula: see text] = 0.0507 L/h. Simulations of 25OHD3 concentration indicated an inverse relationship between 25OHD3 baseline and response, as well as a less than proportional 25OHD3 response. Estimation of assay bias parameters suggested that HPLC-MS and RIA produced similar measurement results, whereas CPBA and CHEMI are over-predictive of 25OHD3 concentration, relative to HPLC-MS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.