Purpose

Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1–100 g.

Methods

A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1–100 g; oncology participants received IVC infusions of 25–100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study.

Results

In both cohorts, IVC exhibited first-order kinetics at doses up to 75 g. At 100 g, maximum concentration (C_max) plateaued in both groups, whereas area under the concentration–time curve (AUC) only plateaued in the healthy group. IVC was primarily excreted through urine. No saturation of clearance was observed; however, the mean 24-h total IVC excretion in urine for all doses was lower in oncology participants (89% of dose) than in healthy participants at 100 g (99%). No significant adverse events were observed; thus, maximum tolerated dose (MTD) was not reached.

Conclusion

IVC followed first-order pharmacokinetics up to 75 g and at up to 100 g had complete renal clearance in 24 h. IVC up to 100 g elicited no adverse effects or significant physiological/biochemical changes and appears to be safe. These data can be used to rectify existing misinformation and to guide future clinical trials.

Registration

ClinicalTrials.gov identifier number NCT01833351.

中文翻译：

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静脉注射维生素 C 的药代动力学评价：经典药代动力学研究

目的

静脉注射维生素 C (IVC) 可用于支持药代动力学数据有限的多种疾病。在此，我们报告了一项针对 IVC 剂量在 1-100 g 范围内的健康志愿者和癌症参与者的药代动力学研究。

方法

在 21 名健康志愿者和 12 名肿瘤学参与者中进行了一项药代动力学研究。健康参与者接受了 1-100 g 的 IVC 输注；肿瘤学参与者接受了 25-100 g 的 IVC 输注。在输注前和输注后 24 小时收集系列血液和完整尿液样本。使用非隔室方法计算药代动力学参数。在研究期间监测不良事件。

结果

在这两个队列中，IVC 在高达 75 g 的剂量下表现出一级动力学。在 100 g 时，两组的_{最大浓度 (Cmax} )均达到稳定状态，而浓度-时间曲线下面积 (AUC) 仅在健康组中达到稳定状态。IVC 主要通过尿液排出。没有观察到清除率饱和；然而，在所有剂量下，肿瘤学参与者的平均 24 小时尿中总 IVC 排泄量（89% 的剂量）低于 100 g 的健康参与者（99%）。没有观察到明显的不良事件；因此，未达到最大耐受剂量（MTD）。

结论

IVC 遵循一级药代动力学，最高 75 g，最高 100 g，在 24 小时内具有完全的肾清除率。高达 100 g 的 IVC 没有引起不良反应或显着的生理/生化变化，并且似乎是安全的。这些数据可用于纠正现有的错误信息并指导未来的临床试验。

登记

ClinicalTrials.gov 标识符号 NCT01833351。