The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Pharmacokinetic Model of Ascorbic Acid in Healthy Male Volunteers During Depletion and Repletion
Abstract
Purpose To develop a new pharmacokinetic model for ascorbic acid (vitamin C) since no previously published model describes ascorbic acid absorption and disposition over a broad physiologic range of doses and plasma concentrations.Methods A new model was developed through exploratory simulations. The model was fitted to pharmacokinetic data obtained from seven healthy volunteers who underwent ascorbic acid depletion then gradual repletion. Concentrations of ascorbic acid were measured in plasma and urine. Final pharmacokinetic model parameter estimates were obtained using nonlinear regression analysis.Results The new model included saturable absorption, distribution and renal tubular reabsorption parameters. The model described ascorbic acid concentrations in plasma, cells, and urine during depletion and gradual repletion phases with a residual error less than 15%.Conclusions The model was useful for obtaining a new understanding of the likely causes for the complex concentration-time profile observed during gradual repletion. At doses of 200 to 2500 mg per day, the plateau in pre-dose concentrations is largely due to apparent saturation of tissue uptake and less a function of oral bioavailability and renal excretion than previously thought.
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“In daily doses of 30–60 mg, almost no vitamin C is excreted in urine within 24 h, while a dose of 100 mg results in 25% of the dose of vitamin C excreted and doses equalling or above 500 mg are almost entirely excreted [55,57].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [57]
In the citing paper
“The Michaelis constant Km for renal reabsorption of vitamin C in relation to its plasma levels was suggested to be 33 µM, which is approximately in line with the maximum plasma levels [57].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [57]
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Cited by
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Vitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention
Padayatty, S. J., Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J.-H., Chen, S., Corpe, C., Dutta, A., Dutta, S. K., et al. (2003) · Journal of the American College of Nutrition · doi:10.1080/07315724.2003.10719272 · Cited by 1,949
Self-citationAscorbic acid: Chemistry, biology and the treatment of cancer
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Vitamin C pharmacokinetics: Implications for oral and intravenous use
Padayatty, S. J., Sun, H., Wang, Y., Riordan, H. D., Hewitt, S. M., Katz, A., Wesley, R. A., & Levine, M. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-140-7-200404060-00010 · Cited by 992
Self-citationRole of antioxidants in prophylaxis and therapy: A pharmaceutical perspective
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Self-citation
Metadata
- Authors
- Graumlich, J. F., Ludden, T. M., Conry-Cantilena, C., Cantilena, L. R., Wang, Y., & Levine, M.
- Affiliations
- Peoria campus of the University of Illinois System (US)
- University of Nebraska Medical Center (US)
- Uniformed Services University of the Health Sciences (US)
- National Institutes of Health (US)
- Corresponding author
- Graumlich, James F.
- Venue
- Pharmaceutical Research
- Published
- 1997-09
- Volume
- 14
- Issue
- 9
- Pages
- 1133-1139
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W1489783301
- Cited by
- 172
- References
- 25
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 12 · 2020: 11 · 2019: 10 · 2018: 5 · 2017: 8 · 2016: 6 · 2015: 9 · 2014: 9 · 2013: 7 · 2012: 9
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (224-88-3002)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-92-0032)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Keywords
- vitamin C, pharmacokinetic modeling, vitamin C depletion, saturable absorption, tubular reabsorption, oral bioavailability, healthy men
- MeSH terms
- Adult, Ascorbic Acid, Biological Availability, Humans, Male, Models, Biological, Prospective Studies
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