Pharmacokinetic data support 6-hourly dosing of intravenous vitamin C to critically ill patients with septic shock

Crit Care Resusc. 2019 Dec;21(4):236-42.


Objectives: To study vitamin C pharmacokinetics in septic shock.

Design: Prospective pharmacokinetic study.

Setting: Two intensive care units.

Participants: Twenty-one patients with septic shock enrolled in a randomised trial of high dose vitamin C therapy in septic shock.

Intervention: Patients received 1.5 g intravenous vitamin C every 6 hours. Plasma samples were obtained before and at 1, 4 and 6 hours after drug administration, and vitamin C concentrations were measured by high performance liquid chromatography.

Main outcome measures: Clearance, volume of distribution, and half-life were calculated using noncompartmental analysis. Data are presented as median (interquartile range [IQR]).

Results: Of the 11 participants who had plasma collected before any intravenous vitamin C administration, two (18%) were deficient (concentrations < 11 μmol/L) and three (27%) had hypovitaminosis C (concentrations between 11 and 23 μmol/L), with a median concentration 28 μmol/L (IQR, 11-44 μmol/L). Volume of distribution was 23.3 L (IQR, 21.9-27.8 L), clearance 5.2 L/h (IQR, 3.3-5.4 L/h), and half-life 4.3 h (IQR, 2.6-7.5 h). For the participants who had received at least one dose of intravenous vitamin C before sampling, T0 concentration was 258 μmol/L (IQR, 162- 301 μmol/L). Pharmacokinetic parameters for subsequent doses were a median volume of distribution 39.9 L (IQR, 31.4-44.4 L), clearance 3.6 L/h (IQR, 2.6-6.5 L/h), and half-life 6.9 h (IQR, 5.7-8.5 h).

Conclusion: Intravenous vitamin C (1.5 g every 6 hours) corrects vitamin C deficiency and hypovitaminosis C and provides an appropriate dosing schedule to achieve and maintain normal or elevated vitamin C levels in septic shock.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / blood
  • Ascorbic Acid / pharmacokinetics*
  • Ascorbic Acid Deficiency / drug therapy*
  • Ascorbic Acid Deficiency / prevention & control
  • Biomarkers / blood
  • Chromatography, High Pressure Liquid
  • Critical Illness / therapy*
  • Dose-Response Relationship, Drug
  • Humans
  • Prospective Studies
  • Shock, Septic / blood
  • Shock, Septic / drug therapy*
  • Shock, Septic / metabolism
  • Vitamins / administration & dosage
  • Vitamins / blood
  • Vitamins / pharmacokinetics*


  • Biomarkers
  • Vitamins
  • Ascorbic Acid