Sebastian J. Padayatty, MRCP, PhD; He Sun, PhD, CBS; Yaohui Wang, MD; Hugh D. Riordan, MD; Stephen M. Hewitt, MD, PhD; Arie Katz, MD; Robert A. Wesley, PhD; Mark Levine, MD
Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, et al. Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Ann Intern Med. 2004;140:533-537. doi: 10.7326/0003-4819-140-7-200404060-00010
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Published: Ann Intern Med. 2004;140(7):533-537.
Vitamin C at high concentrations is toxic to cancer cells in vitro. Early clinical studies of vitamin C in patients with terminal cancer suggested clinical benefit, but 2 double-blind, placebo-controlled trials showed none. However, these studies used different routes of administration.
To determine whether plasma vitamin C concentrations vary substantially with the route of administration.
Dose concentration studies and pharmacokinetic modeling.
Academic medical center.
17 healthy hospitalized volunteers.
Vitamin C plasma and urine concentrations were measured after administration of oral and intravenous doses at a dose range of 0.015 to 1.25 g, and plasma concentrations were calculated for a dose range of 1 to 100 g.
Peak plasma vitamin C concentrations were higher after administration of intravenous doses than after administration of oral doses (P < 0.001), and the difference increased according to dose. Vitamin C at a dose of 1.25 g administered orally produced mean (Â±sd) peak plasma concentrations of 134.8 Â± 20.6 Âµmol/L compared with 885 Â± 201.2 Âµmol/L for intravenous administration. For the maximum tolerated oral dose of 3 g every 4 hours, pharmacokinetic modeling predicted peak plasma vitamin C concentrations of 220 Âµmol/L and 13 400 Âµmol/L for a 50-g intravenous dose. Peak predicted urine concentrations of vitamin C from intravenous administration were 140-fold higher than those from maximum oral doses.
Patient data are not available to confirm pharmacokinetic modeling at high doses and in patients with cancer.
Oral vitamin C produces plasma concentrations that are tightly controlled. Only intravenous administration of vitamin C produces high plasma and urine concentrations that might have antitumor activity. Because efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated.
Plasma vitamin C concentrations are shown as a function of time after the 1.25-g oral or intravenous dose administered at steady state for that dose in 12 persons (3 men, 9 women). Inset: Peak plasma vitamin C concentrations as a function of dose after oral or intravenous administration of vitamin C. Seventeen persons (7 men, 10 women) received doses from 0.015 to 0.1 g, 16 persons (6 men, 10 women) received the 0.2-g dose, 14 persons (6 men, 8 women) received the 0.5-g dose, and 12 persons (3 men, 9 women) received the 1.25-g dose. Persons received each dose while at steady state for that dose.
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