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|Title:||A case of accidental neonatal paracetamol overdose with prolonged half-life and measured metabolites.|
|Authors:||Abadier, Monica;Wong, Anselm;Stathakis, Paul;Singsit, John;Pillay, Melanie;Graudins, Andis|
|Affiliation:||Department of Paediatrics, Dandenong Hospital, Monash Health, Victoria, Australia|
Monash Toxicology Unit and Emergency Medicine Service, Monash Health, Victoria, Australia
SEALS Laboratory, Prince of Wales Hospital, Sydney, Australia
Department of Medicine and Radiology, Centre for Integrated Clinical Care, Melbourne Medical School, University of Melbourne, Melbourne, Australia
Austin Toxicology Service, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine, School of Clinical Sciences, Monash University, Victoria, Australia
|Citation:||Clinical toxicology (Philadelphia, Pa.) 2019; online first: 11 March|
|Abstract:||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. 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. 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.|
|Subjects:||Gut and hepatotoxicity|
|Appears in Collections:||Journal articles|
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