Padayatty Sebastian J, Sun He, Wang Yaohui, Riordan Hugh D, Hewitt Stephen M, Katz Arie, Wesley Robert A, Levine Mark
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.
Ann Intern Med. 2004 Apr 6;140(7):533-7. doi: 10.7326/0003-4819-140-7-200404060-00010.
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 (+/-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.
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.
高浓度维生素C在体外对癌细胞有毒性。早期针对晚期癌症患者的维生素C临床研究显示有临床益处，但两项双盲、安慰剂对照试验未显示出益处。然而，这些研究采用了不同的给药途径。
确定血浆维生素C浓度是否会因给药途径而有显著差异。
剂量浓度研究和药代动力学建模。
学术医疗中心。
17名住院的健康志愿者。
口服和静脉注射剂量范围为0.015至1.25 g后，测量维生素C的血浆和尿液浓度，并计算剂量范围为1至100 g时的血浆浓度。
静脉给药后血浆维生素C峰值浓度高于口服给药后（P < 0.001），且差异随剂量增加而增大。口服1.25 g维生素C产生的平均（±标准差）血浆峰值浓度为134.8 ± 20.6 μmol/L，而静脉给药为885 ± 201.2 μmol/L。对于每4小时最大耐受口服剂量3 g，药代动力学建模预测50 g静脉剂量的血浆维生素C峰值浓度为220 μmol/L和13400 μmol/L。静脉给药后维生素C的预测尿液峰值浓度比最大口服剂量时高140倍。
尚无患者数据可用于确认高剂量及癌症患者的药代动力学建模。
口服维生素C产生的血浆浓度受到严格控制。只有静脉注射维生素C才能产生可能具有抗肿瘤活性的高血浆和尿液浓度。由于仅使用口服给药的临床试验无法判断维生素C治疗的疗效，因此应重新评估维生素C在癌症治疗中的作用。
