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

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.

journal_name

Chest

journal_title

Chest

authors

de Grooth HJ,Manubulu-Choo WP,Zandvliet AS,Spoelstra-de Man AME,Girbes AR,Swart EL,Oudemans-van Straaten HM

doi

10.1016/j.chest.2018.02.025

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

1368-1377

issue

eissn

0012-3692

issn

1931-3543

pii

S0012-3692(18)30393-3

journal_volume

153

pub_type

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