• Suzanne L Parker, Manoj Saxena, John Gowardman, Jeffrey Lipman, John Myburgh, and Jason A Roberts.
• The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia. Electronic address: suzanne.parker@uq.edu.au.
• J Crit Care. 2018 Oct 1; 47: 15-20.

PurposeHigh-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 MethodsA 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.ResultsAll 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-1, 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.ConclusionDue to altered pharmacokinetics, patients experiencing severe TBI may require a higher dose of paracetamol to achieve drug exposure that results in preventing pyrexia.Copyright © 2018 Elsevier Inc. All rights reserved.

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