title: The pharmacokinetic profile of intravenous paracetamol in adult patients undergoing major abdominal surgery.
abstract: BACKGROUND
  Intravenous (IV) paracetamol is commonly used in the postoperative period for the treatment of mild to moderate pain. The main pathways for paracetamol metabolism are glucuronidation, sulfation, and oxidation, accounting for approximately 55%, 30%, and 10% of urinary metabolites, respectively. The aim of this study was to describe the pharmacokinetics of IV paracetamol and its metabolites in adult patients after major abdominal surgery.
  
  
  METHODS
  Twenty patients were given 1 g of paracetamol by IV infusion at induction of anesthesia (Interval 1) and every 6 hours thereafter, with the final dose given at 48-72 hours (Interval 2). Plasma and urine samples were collected for up to 8 hours after infusion for both intervals. The samples were analyzed by high-performance liquid chromatography to determine the amount of paracetamol and its metabolites. The data were modeled in Phoenix WinNonlin using a user-defined ASCII parent-metabolite model with linear disposition, to obtain the estimates for volume of distribution, metabolic and urinary clearance.
  
  
  RESULTS
  Mean (95% confidence interval) metabolic clearance to paracetamol glucuronide increased from 0.06 (0.05-0.08) to 0.14 (0.11-0.18) L · h⁻¹ · kg⁻¹, P value <0.001 and urinary clearance increased from 0.08 (0.07-0.09) to 0.14 (0.10-0.17) L · h⁻¹ · kg⁻¹, P value 0.002. The mean (95% confidence interval) volume of distribution of paracetamol increased from 0.17 (0.12-0.21) to 0.43 (0.27-0.59) L · kg⁻¹, P value 0.032.
  
  
  CONCLUSIONS
  After major abdominal surgery, there were apparent increases in the metabolic conversion to paracetamol glucuronide and its urinary clearance suggesting potential induction of paracetamol glucuronidation.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand. katie.owens@otago.ac.nz
authors.forename: Katie H
authors.initials: KH
authors.lastname: Owens
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Medlicott
authors.forename: Mathew
authors.initials: M
authors.lastname: Zacharias
authors.forename: Neil
authors.initials: N
authors.lastname: Curran
authors.forename: Sree
authors.initials: S
authors.lastname: Chary
authors.forename: Mark
authors.initials: M
authors.lastname: Thompson-Fawcett
authors.forename: David M
authors.initials: DM
authors.lastname: Reith
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000082:Acetaminophen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011184:Postoperative Period
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; C037386:acetaminophen glucuronide