title: Analgesic effect of i.v. paracetamol: possible ceiling effect of paracetamol in postoperative pain.
abstract: BACKGROUND
  Despite the widespread use of paracetamol for many years, the analgesic serum concentrations of paracetamol are unknown. Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied.
  
  
  METHODS
  Sixty-four women undergoing laparoscopic sterilization were included in a double-blind, placebo-controlled, randomized study. Patients were given i.v. propacetamol 40 mg kg(-1) (group H), 20 mg kg(-1) (group I), 10 mg kg(-1) (group L) or placebo after surgery. Alfentanil was available via patient-controlled analgesia (PCA) during the 4-h postoperative study period. The patients' self-reported pain was registered on the visual analog scale (VAS). A pharmacokinetic model was fitted to the paracetamol data.
  
  
  RESULTS
  One to 3 h after injection of propacetamol the alfentanil consumption was significantly (P = 0.01-0.04) higher in the placebo group compared with groups H, I, and L receiving propacetamol. There were no significant differences between the amounts of alfentanil consumed in groups H, I, and L. Initial VAS-scores were moderate (5.4-6.2), and declined significantly (P < 0.0001) over time, with no difference between groups. Paracetamol followed an open two-compartment model with i.v. administration and first order elimination. The estimated concentrations immediately (t = 0) after injection were 56 mg l(-1) (H), 28 mg l(-1) (I) and 14 mg l(-1) (L).
  
  
  CONCLUSIONS
  We showed a significant opioid-sparing effect of paracetamol in the immediate postoperative period. Pharmacokinetic data were in accordance with other studies. Our results suggest that a ceiling effect of paracetamol may be present at i.v. doses of 5 mg kg(-1), i.e. a serum concentration of 14 mg l(-1), which is a lower dose than previously suggested.
authors.affiliation: Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, Copenhagen, Denmark.
authors.forename: T W
authors.initials: TW
authors.lastname: Hahn
authors.forename: T
authors.initials: T
authors.lastname: Mogensen
authors.forename: C
authors.initials: C
authors.lastname: Lund
authors.forename: L S
authors.initials: LS
authors.lastname: Jacobsen
authors.forename: N-C
authors.initials: NC
authors.lastname: Hjortsoe
authors.forename: S N
authors.initials: SN
authors.lastname: Rasmussen
authors.forename: M
authors.initials: M
authors.lastname: Rasmussen
mesh_terms: D000042:Absorption; D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000328:Adult; D015760:Alfentanil / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000758:Anesthesia; D004311:Double-Blind Method; D005260:Female; D013509:Gynecologic Surgical Procedures; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D010535:Laparoscopy; D008875:Middle Aged; D008954:Models, Biological; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D015760:Alfentanil; D000082:Acetaminophen