Pharmacokinetic Evaluation of Intravenous Vitamin C: A Classic Pharmacokinetic Study.

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 (Cmax) 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.

Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects.

We have completed a single ascending dose clinical study of the proposed chemopreventive agent 3,3'-diindolylmethane (DIM). The study agent was nutritional-grade, absorption-enhanced BioResponse 3,3'-diindolylmethane (BR-DIM). We determined the safety, tolerability, and pharmacokinetics of single doses of BR-DIM in drug-free, non-smoking, healthy men and women. Groups of four subjects were enrolled for each dose level. After randomization, one subject in each group received placebo whereas three received active BR-DIM. The doses administered were 50, 100, 150, 200, and 300 mg, with the 300-mg dose repeated in an additional group. No BR-DIM-related adverse effects were reported at doses up to 200 mg. At the 300-mg dose, one of six subjects reported mild nausea and headache and one also reported vomiting. Only the latter effect was judged as probably related to the study agent. Analysis of serial plasma samples showed that only one subject at the 50-mg dose had detectable concentrations of DIM. The single 100-mg dose of BR-DIM resulted in a mean maximum plasma concentration (C(max)) of 32 ng/mL and a mean area under the curve (AUC) of 128 h ng/mL, and a single 200-mg dose produced a mean C(max) of 104 ng/mL and a mean AUC of 553 h ng/mL. The single 300-mg dose of BR-DIM resulted in a mean C(max) of 108 ng/mL and a mean AUC of 532 h ng/mL. We conclude that BR-DIM is well tolerated at single doses of up to 200 mg, and that increasing the dose to 300 mg did not result in an increase in C(max).