Detection and Follow-Up, after Partial Liver Resection, of the Urinary Paracetamol Metabolites by Proton NMR Spectroscopy

作者：Galinski Michel^*; Racine Stephane Xavier; Bossard Anne Elisabeth; Fleyfel Maher; Hamza Lilia; Bouchemal Nadia; Adnet Frederic; Le Moyec Laurence

来源：Pharmacology, 2014, 93(1-2): 18-23.

DOI：10.1159/000357095

• Partial liver resection
• Proton NMR spectroscopy
• Paracetamol
• Metabolites

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 degrees 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.

• 出版日期2014