Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use

作者：Sebastian J. Padayatty, He Sun, Yaohui Wang, Hugh D. Riordan, Stephen M. Hewitt, Arie Katz, Robert Wesley, Mark Levine · 发表于：Annals of Internal Medicine · 年份：2004 · DOI：10.7326/0003-4819-140-7-200404060-00010 · 被引用次数：982 · 研究领域：Vitamin C and Antioxidants Research、Vitamin K Research Studies、Vitamin D Research Studies

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. DESIGN: Dose concentration studies and pharmacokinetic modeling. SETTING: Academic medical center. PARTICIPANTS: 17 healthy hospitalized volunteers. MEASUREMENTS: 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 th...