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Pharmacokinetic Model of Ascorbic Acid in Healthy Male Volunteers During Depletion and Repletion

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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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Authors and Affiliations

  1. Department of Biomedical and Therapeutic Sciences University of Illinois College of Medicine at Peoria, Peoria, Illinois, 61656-1649

    James F. Graumlich

  2. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska

    Thomas M. Ludden (Parke-Davis Professor and Chair)

  3. Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland

    Cathy Conry-Cantilena

  4. Division of Clinical Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland

    Louis R. Cantilena Jr (Chief)

  5. Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

    Yaohui Wang

  6. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

    Mark Levine (Director, Intramural Nutrition Program, and Chief, Molecular and Clinical Nutrition Section)

Authors
  1. James F. Graumlich
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  2. Thomas M. Ludden
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  3. Cathy Conry-Cantilena
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  4. Louis R. Cantilena Jr
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  5. Yaohui Wang
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  6. Mark Levine
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Correspondence to James F. Graumlich.

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Graumlich, J.F., Ludden, T.M., Conry-Cantilena, C. et al. Pharmacokinetic Model of Ascorbic Acid in Healthy Male Volunteers During Depletion and Repletion. Pharm Res 14, 1133–1139 (1997). https://doi.org/10.1023/A:1012186203165

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  • DOI: https://doi.org/10.1023/A:1012186203165

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