Vitamin C Pharmacokinetics in Critically Ill Patients: A Randomized Trial of Four IV Regimens - PubMed (original) (raw)

Randomized Controlled Trial

. 2018 Jun;153(6):1368-1377.

doi: 10.1016/j.chest.2018.02.025. Epub 2018 Mar 6.

Affiliations

Randomized Controlled Trial

Vitamin C Pharmacokinetics in Critically Ill Patients: A Randomized Trial of Four IV Regimens

Harm-Jan de Grooth et al. Chest. 2018 Jun.

Abstract

Background: Early high-dose IV vitamin C is being investigated as adjuvant therapy in patients who are critically ill, but the optimal dose and infusion method are unclear. The primary aim of this study was to describe the dose-plasma concentration relationship and safety of four different dosing regimens.

Methods: This was a four-group randomized pharmacokinetic trial. Patients who were critically ill with multiple organ dysfunction were randomized to receive 2 or 10 g/d vitamin C as a twice daily bolus infusion or continuous infusion for 48 h. End points were plasma vitamin C concentrations during 96 h, 12-h urine excretion of vitamin C, and oxalate excretion and base excess. A population pharmacokinetic model was developed using NONMEM.

Results: Twenty patients were included. A two-compartment pharmacokinetic model with creatinine clearance and weight as independent covariates described all four regimens best. With 2 g/d bolus, plasma vitamin C concentrations at 1 h were 29 to 50 mg/L and trough concentrations were 5.6 to 16 mg/L. With 2 g/d continuous, steady-state concentrations were 7 to 37 mg/L at 48 h. With 10 g/d bolus, 1-h concentrations were 186 to 244 mg/L and trough concentrations were 14 to 55 mg/L. With 10 g/d continuous, steady-state concentrations were 40 to 295 mg/L at 48 h. Oxalate excretion and base excess were increased in the 10 g/d dose. Forty-eight hours after discontinuation, plasma concentrations declined to hypovitaminosis levels in 15% of patients.

Conclusions: The 2 g/d dose was associated with normal plasma concentrations, and the 10 g/d dose was associated with supranormal plasma concentrations, increased oxalate excretion, and metabolic alkalosis. Sustained therapy is needed to prevent hypovitaminosis.

Trial registry: ClinicalTrials.gov; No.: NCT02455180; URL: www.clinicaltrials.gov.

Keywords: ascorbate; ascorbic acid; clinical trial; intensive care; pharmacology.

Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

PubMed Disclaimer

Comment in

Publication types

MeSH terms

Substances

LinkOut - more resources