Population pharmacokinetics of intravenous paracetamol in critically ill patients with traumatic brain injury.

Suzanne L Parker, Manoj Saxena, John Gowardman, Jeffrey Lipman, John Myburgh, Jason A Roberts

Journal: Journal of critical care 2019;47():15-20

PMID: 29883885

Full Text on Elsevier Science View on PubMed

Abstract

PURPOSE

High-dose paracetamol (6 g/day) is a low-cost intervention that may prevent pyrexia. The purpose of this study was to describe the pharmacokinetics of high-dose intravenous paracetamol, in patients with traumatic brain injury (TBI).

MATERIALS AND METHODS

A clinical pharmacokinetic study in adult patients with TBI was performed as a sub-study to a prospective, phase 2B, randomized placebo-controlled study (PARITY). Patients received 1 g of intravenous paracetamol or 0.9% sodium chloride every 4 h for 72 h.

RESULTS

All patients were included in the pharmacokinetic sub-study. The mean age, weight and area under the concentration-time curve for the sampled dosing interval were 34.5 yr, 82.3 kg and 39.9 ± 19.8 mg.h/L, respectively. The concentrations observed in the study patients were well below the threshold of toxicity and there was no evidence of accumulation of paracetamol. Paracetamol clearance was found to be high and variable (25.7 L.h, coefficient of variation (CV) 40.9%), and a wide range of volume of distribution observed (27.6 L, CV 30.6%). A relationship between lower Glasgow coma scores and higher clearance of paracetamol was observed.

CONCLUSION

Due to altered pharmacokinetics, patients experiencing severe TBI may require a higher dose of paracetamol to achieve drug exposure that results in preventing pyrexia.

Address: The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia. Electronic address: [email protected].; Department of Intensive Care Medicine, St. George Hospital Clinical School, University of New South Wales, Australia.; Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, Australia.; The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Australia.; The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, Australia; Centre of Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Australia; Department of Pharmacy, Royal Brisbane & Women's Hospital, Brisbane, Australia.

DOI: 10.1016/j.jcrc.2018.05.016

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MeSH Terms: Acetaminophen, Adult, Antipyretics, Area Under Curve, Brain Injuries, Traumatic, Critical Illness, Double-Blind Method, Female, Fever, Humans, Infusions, Intravenous, Male, Prospective Studies