Detection and follow-up, after partial liver resection, of the urinary paracetamol metabolites by proton NMR spectroscopy

Pharmacology. 2014;93(1-2):18-23. doi: 10.1159/000357095. Epub 2014 Jan 8.

Abstract

Background: Combination drug therapy is often used to achieve optimal analgesia in surgery. Paracetamol can be used as one component of an analgesic regime following hepatic resection.

Objective: This study was designed to investigate paracetamol and its metabolites by proton NMR spectroscopy in patient urine and to assess whether N-acetyl-p-benzoquinone imine (NAPQI, a hepatotoxic metabolite) formation is increased after liver resection.

Method: We studied the excretion of acetaminophen and its metabolites by 5 patients who were operated on for partial liver resection by proton NMR spectroscopy. As an intravenous infusion 1 g of paracetamol was given over 15 min every 6 h during 48 h. The first injection was given in the operating theatre after liver resection was completed. Urine samples were collected before injection (T1) and 24 and 48 h after the first injection (T2 and T3); the samples were frozen and kept at -20°C up to the analysis by NMR spectroscopy.

Results: Metabolites of the paracetamol were detected for all patients. Among the discerned metabolites, 4 were identified as metabolites of paracetamol: paracetamol glucuronide, paracetamol sulfate, N-acetyl-L-cysteinyl paracetamol (metabolite of NAPQI) and paracetamol. Their ratios, respectively, were: 46-82.9, 12.6-30.0, 0.5-5.5 and 1.43-3.54%.

Conclusion: This study showed that there was no increase in the formation of toxic metabolite (NAPQI) after treatment with paracetamol in these few cases of liver resections. A larger study is necessary to confirm these results.

Publication types

  • Observational Study

MeSH terms

  • Acetaminophen / analogs & derivatives
  • Acetaminophen / pharmacokinetics*
  • Acetaminophen / urine
  • Analgesics / pharmacokinetics*
  • Analgesics / urine
  • Benzoquinones / urine
  • Female
  • Humans
  • Imines / urine
  • Liver / metabolism*
  • Liver / surgery*
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged

Substances

  • Analgesics
  • Benzoquinones
  • Imines
  • Acetaminophen
  • acetaminophen glucuronide
  • N-acetyl-4-benzoquinoneimine
  • acetaminophen sulfate ester