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

Abstract

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 halflife 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.