title: Detection and follow-up, after partial liver resection, of the urinary paracetamol metabolites by proton NMR spectroscopy.
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.
  
  
  METHODS
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: APHP, Urgences, SAMU 93, Hôpital Avicenne, Bobigny, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Galinski
authors.forename: Stephane-Xavier
authors.initials: SX
authors.lastname: Racine
authors.forename: Anne-Elisabeth
authors.initials: AE
authors.lastname: Bossard
authors.forename: Maher
authors.initials: M
authors.lastname: Fleyfel
authors.forename: Lilia
authors.initials: L
authors.lastname: Hamza
authors.forename: Nadia
authors.initials: N
authors.lastname: Bouchemal
authors.forename: Frédéric
authors.initials: F
authors.lastname: Adnet
authors.forename: Laurence
authors.initials: L
authors.lastname: Le Moyec
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000652:urine; D000700:Analgesics / Q000493:pharmacokinetics* / Q000652:urine; D016227:Benzoquinones / Q000652:urine; D005260:Female; D006801:Humans; D007097:Imines / Q000652:urine; D008099:Liver / Q000378:metabolism* / Q000601:surgery*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged
chemical_list: D000700:Analgesics; D016227:Benzoquinones; D007097:Imines; D000082:Acetaminophen; C037386:acetaminophen glucuronide; C028473:N-acetyl-4-benzoquinoneimine; C045667:acetaminophen sulfate ester