caa a22 4500 477126103 CHVBK 20180405111650.0 cr unu---uuuuu 170330e19970901xx s 000 0 eng 10.1023/A:1012186203165 doi (NATIONALLICENCE)springer-10.1023/A:1012186203165 Pharmacokinetic Model of Ascorbic Acid in Healthy Male Volunteers During Depletion and Repletion [Elektronische Daten] [James Graumlich, Thomas Ludden, Cathy Conry-Cantilena, Louis Cantilena Jr, Yaohui Wang, Mark Levine] 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. Plenum Publishing Corporation, 1997 ascorbic acid nationallicence pharmacokinetics nationallicence human nationallicence models— theoretical nationallicence models—nonlinear nationallicence bioavailability nationallicence ascorbic acid deficiency nationallicence Graumlich James Department of Biomedical and Therapeutic Sciences University of Illinois College of Medicine at Peoria, 61656-1649, Peoria, Illinois aut Ludden Thomas Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska aut Conry-Cantilena Cathy Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland aut Cantilena Jr Louis Division of Clinical Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland aut Wang Yaohui Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland aut Levine Mark National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1133-1139 0724-8741 14:9<1133 1997 14 11095 https://doi.org/10.1023/A:1012186203165 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012186203165 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Graumlich James Department of Biomedical and Therapeutic Sciences University of Illinois College of Medicine at Peoria, 61656-1649, Peoria, Illinois aut NATIONALLICENCE 700 1- Ludden Thomas Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska aut NATIONALLICENCE 700 1- Conry-Cantilena Cathy Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland aut NATIONALLICENCE 700 1- Cantilena Jr Louis Division of Clinical Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland aut NATIONALLICENCE 700 1- Wang Yaohui Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland aut NATIONALLICENCE 700 1- Levine Mark National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1133-1139 0724-8741 14:9<1133 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer