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

Elizabeth P Hudson, Jake Tb Collie, Tomoko Fujii, Nora Luethi, Andrew A Udy, Sarah Doherty, Glenn Eastwood, Fumitaka Yanase, Thummaporn Naorungroj, Laurent Bitker, Yasmine Ali Abdelhamid, Ronda F Greaves, Adam M Deane, Rinaldo Bellomo
Critical Care and Resuscitation: Journal of the Australasian Academy of Critical Care Medicine 2019, 21 (4): 236-42
31778629

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.

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