Vitamin C pharmacokinetics: implications for oral and intravenous use.
BACKGROUND
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.


OBJECTIVE
To determine whether plasma vitamin C concentrations vary substantially with the route of administration.


METHODS
Dose concentration studies and pharmacokinetic modeling.


METHODS
Academic medical center.


METHODS
17 healthy hospitalized volunteers.


METHODS
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.


RESULTS
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 (+/-sd) peak plasma concentrations of 134.8 +/- 20.6 micromol/L compared with 885 +/- 201.2 micromol/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 micromol/L and 13 400 micromol/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.


CONCLUSIONS
Patient data are not available to confirm pharmacokinetic modeling at high doses and in patients with cancer.


CONCLUSIONS
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.
Padayatty
Sebastian J
SJ
National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institut, and the Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1372, USA.
Sun
He
H
Wang
Yaohui
Y
Riordan
Hugh D
HD
Hewitt
Stephen M
SM
Katz
Arie
A
Wesley
Robert A
RA
Levine
Mark
M
D000284:Administration, Oral; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D012016:Reference Values
D000970:Antineoplastic Agents; D001205:Ascorbic Acid