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

Elizabeth P. Hudson, Jake T.B. 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

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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 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.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalCritical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine
Volume21
Issue number4
Publication statusPublished - Dec 2019

Cite this

Hudson, Elizabeth P. ; Collie, Jake T.B. ; Fujii, Tomoko ; Luethi, Nora ; Udy, Andrew A. ; Doherty, Sarah ; Eastwood, Glenn ; Yanase, Fumitaka ; Naorungroj, Thummaporn ; Bitker, Laurent ; Abdelhamid, Yasmine Ali ; Greaves, Ronda F. ; Deane, Adam M. ; Bellomo, Rinaldo. / Pharmacokinetic data support 6-hourly dosing of intravenous vitamin C to critically ill patients with septic shock. In: Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine. 2019 ; Vol. 21, No. 4. pp. 236-242.
@article{36fc6f3085ff499792429ac254ee47f2,
title = "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 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.",
author = "Hudson, {Elizabeth P.} and Collie, {Jake T.B.} and Tomoko Fujii and Nora Luethi and Udy, {Andrew A.} and Sarah Doherty and Glenn Eastwood and Fumitaka Yanase and Thummaporn Naorungroj and Laurent Bitker and Abdelhamid, {Yasmine Ali} and Greaves, {Ronda F.} and Deane, {Adam M.} and Rinaldo Bellomo",
year = "2019",
month = "12",
language = "English",
volume = "21",
pages = "236--242",
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Pharmacokinetic data support 6-hourly dosing of intravenous vitamin C to critically ill patients with septic shock. / Hudson, Elizabeth P.; Collie, Jake T.B.; Fujii, Tomoko; Luethi, Nora; Udy, Andrew A.; Doherty, Sarah; Eastwood, Glenn; Yanase, Fumitaka; Naorungroj, Thummaporn; Bitker, Laurent; Abdelhamid, Yasmine Ali; Greaves, Ronda F.; Deane, Adam M.; Bellomo, Rinaldo.

In: Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine, Vol. 21, No. 4, 12.2019, p. 236-242.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Pharmacokinetic data support 6-hourly dosing of intravenous vitamin C to critically ill patients with septic shock

AU - Hudson, Elizabeth P.

AU - Collie, Jake T.B.

AU - Fujii, Tomoko

AU - Luethi, Nora

AU - Udy, Andrew A.

AU - Doherty, Sarah

AU - Eastwood, Glenn

AU - Yanase, Fumitaka

AU - Naorungroj, Thummaporn

AU - Bitker, Laurent

AU - Abdelhamid, Yasmine Ali

AU - Greaves, Ronda F.

AU - Deane, Adam M.

AU - Bellomo, Rinaldo

PY - 2019/12

Y1 - 2019/12

N2 - 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.

AB - 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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UR - https://cicm.org.au/Resources/Publications/Journal/2010-2020

M3 - Article

C2 - 31778629

AN - SCOPUS:85075798179

VL - 21

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EP - 242

JO - Critical Care and Resuscitation

JF - Critical Care and Resuscitation

SN - 1441-2772

IS - 4

ER -