European Journal of Clinical Pharmacology

, Volume 74, Issue 2, pp 253–253 | Cite as

In reply

  • Anselm Wong
  • Cornelia B. Landersdorfer
  • Andis Graudins
Letter to the Editor
  • 201 Downloads

To the editor:

Thank you for the interest in our paper [1]. We agree that this study represents a population pharmacokinetic model based on healthy volunteers and that acetylcysteine concentrations may differ within the poisoned population. Currently, there are no suitable pharmacokinetic studies of acetylcysteine concentrations in poisoned patients that can be used to derive these models. These simulations aim to demonstrate acetylcysteine concentrations that may be achieved when modifying the existing regimen and help inform but not replace clinical trials.

The standard three bag regimen that has been used for the last four decades was designed as a “one size fits all” model. At the time, dosing was based on a number of assumptions without the use of population pharmacokinetic models and not based on randomised controlled trials. Clearly, there are individuals that may still develop hepatotoxicity despite receiving acetylcysteine within 8 h [2, 3]. In addition, there is a significant cohort of patients who are at low risk of hepatotoxicity who simply may not require a prolonged course of acetylcysteine [4, 5]. While our study provides some theoretical data on expected acetylcysteine concentrations with various novel regimens, refining and validating risk stratification techniques [6] as well as further acetylcysteine regimen efficacy studies are needed to optimise the management of the paracetamol poisoned patient.

Notes

Compliance with ethical standards

Competing interests

The authors declare that they have no conflict of interest.

References

  1. 1.
    Wong A, Landersdorfer C, Graudins A (2017) Pharmacokinetic modelling of modified acetylcysteine infusion regimens used in the treatment of paracetamol poisoning. Eur J Clin Pharmacol 73(9):1103–1110.  https://doi.org/10.1007/s00228-017-2277-4 CrossRefPubMedGoogle Scholar
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    Cairney DG, Beckwith HK, Al-Hourani K, Eddleston M, Bateman DN, Dear JW (2016) Plasma paracetamol concentration at hospital presentation has a dose-dependent relationship with liver injury despite prompt treatment with intravenous acetylcysteine. Clin Toxicol 54(5):405–410.  https://doi.org/10.3109/15563650.2016.1159309 CrossRefGoogle Scholar
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    Bateman DN, Dear JW, Thanacoody HK, Thomas SH, Eddleston M, Sandilands EA et al (2014) Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet 383(9918):697–704.  https://doi.org/10.1016/S0140-6736(13)62062-0 CrossRefPubMedGoogle Scholar
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    Wong A, Gunja N, McNulty R, Graudins A (2017) Analysis of an 8-hour acetylcysteine infusion protocol for repeated supratherapeutic ingestion (RSTI) of paracetamol. Clin Toxicol:1–5Google Scholar
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    Wong A, Graudins A (2017) Risk prediction of hepatotoxicity in paracetamol poisoning. Clin Toxicol 55(8):879–892.  https://doi.org/10.1080/15563650.2017.1317349 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.School of Clinical Sciences, Department of MedicineMonash UniversityMelbourneAustralia
  2. 2.Victorian Poisons Information Centre and Austin Toxicology ServiceAustin HospitalHeidelbergAustralia
  3. 3.Centre for Medicine and Safety Use, Faculty of Pharmacy and Pharmaceutical SciencesMonash UniversityParkvilleAustralia
  4. 4.Monash Emergency Research CollaborativeMonash HealthMelbourneAustralia

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