title: The pharmacokinetics and analgesic efficacy of larger dose rectal acetaminophen (40 mg/kg) in adults: a double-blinded, randomized study.
abstract: Analgesic acetaminophen plasma concentrations are not known. We investigated in a randomized, double-blinded study the pharmacokinetics and analgesic efficacy of small- (AS; 20 mg. kg(-1)) and larger- (AL; 40 mg/kg) dose rectal acetaminophen and compared it with the combination (C) of rectal diclofenac (100 mg) and acetaminophen (20 mg/kg) in 65 women undergoing hysterectomy. Suppositories were administered after the induction of a standardized general anesthesia. Pain (measured by using a 10-cm visual analog scale) and morphine consumption (patient-controlled analgesia) were repeatedly assessed for 24 h. Acetaminophen plasma concentrations were measured by using a fluorescence polarization immunoassay. Antipyretic plasma concentrations (10-20 mg/L) after 40 mg/kg acetaminophen were not associated with improved analgesia or decreased opioid requirements; 20 mg/kg acetaminophen produced subtherapeutic plasma levels (<10 mg/L). Maximal plasma concentrations of 17.2 and 10.4 mg/L (P < 0.01, analysis of variance) were achieved after 4.2 and 3.6 h for the AL and AS groups, respectively. The only difference in clinical outcome was lower visual analog scale scores after acetaminophen/diclofenac (C 2.0 versus AS 3.2 and AL 3.4) 4 h after the induction (P < 0.05, analysis of variance). Acetaminophen pharmacokinetics in adults were similar to those observed in children. Analgesic plasma concentrations are likely to be higher than antipyretic plasma levels, which were only attained after twice the recommended rectal dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis.
  
  
  CONCLUSIONS
  Acetaminophen pharmacokinetics were comparable in adults and children. Plasma concentrations known to reduce fever did not produce better pain relief and were only achieved after twice the conventional dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Charité University Hospital, Humboldt University, Berlin, Germany.
authors.forename: D H
authors.initials: DH
authors.lastname: Beck
authors.forename: M R
authors.initials: MR
authors.lastname: Schenk
authors.forename: K
authors.initials: K
authors.lastname: Hagemann
authors.forename: U R
authors.initials: UR
authors.lastname: Doepfmer
authors.forename: W J
authors.initials: WJ
authors.lastname: Kox
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000627:therapeutic use*; D000285:Administration, Rectal; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D019540:Area Under Curve; D004008:Diclofenac / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D013256:Steroids; D013488:Suppositories
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D013256:Steroids; D013488:Suppositories; D004008:Diclofenac; D000082:Acetaminophen