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Cited by 172Vitamin C and Antioxidants ResearchAntioxidant Activity and Oxidative StressPhytochemicals and Antioxidant Activities

Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion

Graumlich, James F., Ludden, Thomas M., Conry-Cantilena, Cathy, Cantilena, Louis R., Wang, Yaohui, Levine, Mark·1997·Pharmaceutical Research
DOI 10.1023/a:1012186203165
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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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Crossref · 10.1023/a:1012186203165

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  • In daily doses of 30-60 mg, almost no vitamin C is excreted in urine within 24 h; a dose of 100 mg results in 25% of the dose excreted; doses equalling or above 500 mg are almost entirely excreted.

    “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]

  • The Michaelis constant Km for renal reabsorption of vitamin C in relation to its plasma levels was suggested to be 33 μM, approximately in line with maximum plasma levels.

    “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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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.
ORCID
Venue
Pharmaceutical Research
Publisher
Springer Science and Business Media LLC
Published
1997-09
Volume
14
Issue
9
Pages
1133-1139
ISSN
  • 0724-8741 (ISSN-L)
  • 1573-904X
DOI
10.1023/a:1012186203165
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 › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Biochemistry › 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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