Intravenous paracetamol is commonly used in the post operative period for the treatment of mild to moderate pain following surgery. The aim of the present study was to investigate the effect of major bowel surgery on paracetamol glucuronidation and sulphation. Patients were given 1 g intravenous paracetamol (10mg/mL) infused over 10 min on the morning of surgery, and again 3 days later. Plasma samples were collected for up to 8 h after infusion and urine samples were collected for 6 h. Twenty patients were enrolled in the study and complete data for plasma and urine were available for both doses for 10 patients who were included in the analysis; five of the patients were men, the median age (range) was 67.5 years (57–85) and the median weight (range) was 71 kg (57–101). Plasma and urine samples were analysed by high-pressure liquid chromatography to determine the amount of paracetamol and its glucuronide and sulphate metabolites. Plasma and urine data for paracetamol, paracetamol-glucuronide and paracetamol-sulphate were modelled using a user defined ASCII parent-metabolite model with linear disposition. Initial parameter estimates were estimated from literature values [1-3]. There was no significant change in paracetamol glucuronidation after surgery. The mean (95% CI) metabolic clearance of glucuronide (CLMG) preoperative 2.34 (1.50–3.17) L•h-1•70kg-1 and 3.30 (1.50-5.10) L•h-1•70kg-1 after surgery, p-value 0.381; and urinary clearance (CLEG) preoperative 0.75 (0.51–0.99) L•h-1•70kg-1 and 0.99 (0.18–1.79) L•h-1•70kg-1 after surgery, p-value 0.586. There was however, a statistically significant increase in paracetamol sulphation following surgery. The mean (95% CI) metabolic clearance of sulphate (CLMS) preoperative 4.47 (3.40–5.55) L•h-1•70kg-1 and 10.05 (7.76–13.34) L•h-1•70kg-1 after surgery, p-value 0.003; and urinary clearance of sulphate (CLES) preoperative 2.99 (2.33–3.64) L•h-1•70kg-1 and 9.91(6.83–12.99) L•h-1•70kg-1 after surgery, p-value 0.002. These results indicate that while paracetamol glucuronidation appears to be unchanged following major bowel surgery, there is an apparent increase in paracetamol sulphation.
References:
- Wurthwein G, Koling S, Reich A, Hempel G, Schulze-Westhoff P, Pinheiro PV, et al. Pharmacokinetics of intravenous paracetamol in children and adolescents under major surgery. European Journal of Clinical Pharmacology2005 Feb;60(12):883-8.
- Van Der Marel CD, Anderson BJ, Van Lingen RA, Holford NHG, Pluim MAL, Jansman FGA, et al. Paracetamol and metabolite pharmacokinetics in infants. European Journal of Clinical Pharmacology2003 01;59(3):243-51.
- Reith D, Medlicott NJ, Kumara De Silva R, Yang L, Hickling J, Zacharias M. Simultaneous modelling of the michaelis-menten kinetics of paracetamol sulphation and glucuronidation. Clinical and Experimental Pharmacology and Physiology2009 January;36(1):35-42.