A case of accidental neonatal paracetamol overdose with prolonged half-life and measured metabolites

Monica Abadier, Anselm Wong, Paul Stathakis, John Singsit, Melanie Pillay, Andis Graudins

Research output: Contribution to journalArticleOtherpeer-review

Abstract

Introduction: Limited data exist regarding paracetamol metabolism after overdose in the neonate. We report a case of repeated supratherapeutic overdose in a neonate with paracetamol metabolite concentrations. Case report: A 10-day-old male neonate presented to hospital after repeated supratherapeutic dosing of paracetamol. Paracetamol concentration 19.5 h post-last dose was 381 μmol/L and 236 μmol/L, 9 h later. Initial alanine aminotransferase (ALT) was normal (18 IU/L) and total bilirubin was 262 μmol/L (N < 300). Acetylcysteine infusion was commenced and ceased 27 h later, when serum paracetamol was undetectable and alanine aminotransferase remained normal. Initial paracetamol elimination half-life was 14.5 h. Analysis of serum paracetamol metabolites showed paracetamol-glucuronide was the major metabolite on presentation (64%). After acetylcysteine was commenced, paracetamol concentration fell, serum bilirubin increased, and paracetamol-sulfate represented a larger proportion of total metabolites (72%). Notably, paracetamol cytochrome (CYP450), cysteine- and mercapturate-conjugates, represented 21% of total measured metabolites on presentation. Conclusion: Repeated supratherapeutic ingestion of paracetamol in the neonate was associated with prolonged elimination half-life. Of note, this was in the presence of unconjugated hyperbilirubinaemia. CYP450 metabolism of paracetamol did not appear to be reduced in this neonate when compared to paracetamol metabolite ratios in older age groups.
Original languageEnglish
Number of pages3
JournalClinical Toxicology
DOIs
Publication statusAccepted/In press - 2019

Cite this

@article{d201721880db42f38d81cc07751f3168,
title = "A case of accidental neonatal paracetamol overdose with prolonged half-life and measured metabolites",
abstract = "Introduction: Limited data exist regarding paracetamol metabolism after overdose in the neonate. We report a case of repeated supratherapeutic overdose in a neonate with paracetamol metabolite concentrations. Case report: A 10-day-old male neonate presented to hospital after repeated supratherapeutic dosing of paracetamol. Paracetamol concentration 19.5 h post-last dose was 381 μmol/L and 236 μmol/L, 9 h later. Initial alanine aminotransferase (ALT) was normal (18 IU/L) and total bilirubin was 262 μmol/L (N < 300). Acetylcysteine infusion was commenced and ceased 27 h later, when serum paracetamol was undetectable and alanine aminotransferase remained normal. Initial paracetamol elimination half-life was 14.5 h. Analysis of serum paracetamol metabolites showed paracetamol-glucuronide was the major metabolite on presentation (64{\%}). After acetylcysteine was commenced, paracetamol concentration fell, serum bilirubin increased, and paracetamol-sulfate represented a larger proportion of total metabolites (72{\%}). Notably, paracetamol cytochrome (CYP450), cysteine- and mercapturate-conjugates, represented 21{\%} of total measured metabolites on presentation. Conclusion: Repeated supratherapeutic ingestion of paracetamol in the neonate was associated with prolonged elimination half-life. Of note, this was in the presence of unconjugated hyperbilirubinaemia. CYP450 metabolism of paracetamol did not appear to be reduced in this neonate when compared to paracetamol metabolite ratios in older age groups.",
author = "Monica Abadier and Anselm Wong and Paul Stathakis and John Singsit and Melanie Pillay and Andis Graudins",
note = "DOI 10.1080/15563650.2019.1587450",
year = "2019",
doi = "10.1080/15563650.2019.1587450",
language = "English",
journal = "Clinical Toxicology",
issn = "1556-3650",
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A case of accidental neonatal paracetamol overdose with prolonged half-life and measured metabolites. / Abadier, Monica ; Wong, Anselm; Stathakis, Paul ; Singsit, John ; Pillay, Melanie; Graudins, Andis.

In: Clinical Toxicology, 2019.

Research output: Contribution to journalArticleOtherpeer-review

TY - JOUR

T1 - A case of accidental neonatal paracetamol overdose with prolonged half-life and measured metabolites

AU - Abadier, Monica

AU - Wong, Anselm

AU - Stathakis, Paul

AU - Singsit, John

AU - Pillay, Melanie

AU - Graudins, Andis

N1 - DOI 10.1080/15563650.2019.1587450

PY - 2019

Y1 - 2019

N2 - Introduction: Limited data exist regarding paracetamol metabolism after overdose in the neonate. We report a case of repeated supratherapeutic overdose in a neonate with paracetamol metabolite concentrations. Case report: A 10-day-old male neonate presented to hospital after repeated supratherapeutic dosing of paracetamol. Paracetamol concentration 19.5 h post-last dose was 381 μmol/L and 236 μmol/L, 9 h later. Initial alanine aminotransferase (ALT) was normal (18 IU/L) and total bilirubin was 262 μmol/L (N < 300). Acetylcysteine infusion was commenced and ceased 27 h later, when serum paracetamol was undetectable and alanine aminotransferase remained normal. Initial paracetamol elimination half-life was 14.5 h. Analysis of serum paracetamol metabolites showed paracetamol-glucuronide was the major metabolite on presentation (64%). After acetylcysteine was commenced, paracetamol concentration fell, serum bilirubin increased, and paracetamol-sulfate represented a larger proportion of total metabolites (72%). Notably, paracetamol cytochrome (CYP450), cysteine- and mercapturate-conjugates, represented 21% of total measured metabolites on presentation. Conclusion: Repeated supratherapeutic ingestion of paracetamol in the neonate was associated with prolonged elimination half-life. Of note, this was in the presence of unconjugated hyperbilirubinaemia. CYP450 metabolism of paracetamol did not appear to be reduced in this neonate when compared to paracetamol metabolite ratios in older age groups.

AB - Introduction: Limited data exist regarding paracetamol metabolism after overdose in the neonate. We report a case of repeated supratherapeutic overdose in a neonate with paracetamol metabolite concentrations. Case report: A 10-day-old male neonate presented to hospital after repeated supratherapeutic dosing of paracetamol. Paracetamol concentration 19.5 h post-last dose was 381 μmol/L and 236 μmol/L, 9 h later. Initial alanine aminotransferase (ALT) was normal (18 IU/L) and total bilirubin was 262 μmol/L (N < 300). Acetylcysteine infusion was commenced and ceased 27 h later, when serum paracetamol was undetectable and alanine aminotransferase remained normal. Initial paracetamol elimination half-life was 14.5 h. Analysis of serum paracetamol metabolites showed paracetamol-glucuronide was the major metabolite on presentation (64%). After acetylcysteine was commenced, paracetamol concentration fell, serum bilirubin increased, and paracetamol-sulfate represented a larger proportion of total metabolites (72%). Notably, paracetamol cytochrome (CYP450), cysteine- and mercapturate-conjugates, represented 21% of total measured metabolites on presentation. Conclusion: Repeated supratherapeutic ingestion of paracetamol in the neonate was associated with prolonged elimination half-life. Of note, this was in the presence of unconjugated hyperbilirubinaemia. CYP450 metabolism of paracetamol did not appear to be reduced in this neonate when compared to paracetamol metabolite ratios in older age groups.

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DO - 10.1080/15563650.2019.1587450

M3 - Article

JO - Clinical Toxicology

JF - Clinical Toxicology

SN - 1556-3650

ER -