title: High-dose rectal and oral acetaminophen in postoperative patients--serum and saliva concentrations.
abstract: BACKGROUND
  The primary purpose of the study was to examine the absorption of acetaminophen by measuring serum and saliva concentrations produced by a standard postoperative acetaminophen dosing regimen and secondary to examine the correlation between saliva and serum concentrations of acetaminophen after rectal and oral dosing.
  
  
  METHODS
  Twenty-four women, aged 18-60 years, scheduled for minor gynaecological laparoscopic surgery were studied. Patients received acetaminophen 2000 mg suppositories after surgery and oral doses of 1000 mg at 4 and 8 h postoperatively. Alfentanil was available via patient-controlled analgesia. Saliva and blood samples were collected postoperatively.
  
  
  RESULTS
  At 1, 2, 3, and 4 h after rectal dosing the saliva concentrations (mean+/-SD) were 15.2+/-5.9 micromol/l, 33.7+/-12.5 micromol/l, 45.5+/-19.1 micromol/l, and 55.4+/-23.1 micromol/l, respectively. The serum concentrations at 2 and 4 h were 31.0+/-11.2 micromol/l and 54.8+/-23.8 micromol/l, respectively. Additional oral dosing resulted in saliva concentrations at 5, 8, and 9 h of 99.7+/-49.5 micromol/l, 106.9+/-31.7 micromol/l, and 139.3+/-55.4 micromol/l, respectively, with coincident serum concentrations of 100.1 +/- 50.2 micromol/l, 105.6+/-29.0 micromol/l, and 141.2+/-52.1 micromol/l. After rectal dosing the linear regression resulted in r2=0.96, P<0.001 and saliva/ serum-ratio=0.99. After additional oral dosing the outcome of linear regression was: r2=0.90, P<0.001 and saliva/serum-ratio= 1.00.
  
  
  CONCLUSIONS
  The slow and ongoing absorption process resulting in no maximum concentration within 4 h after administration of 2000 mg acetaminophen suppositories makes this rectal regimen therapeutically irrational for treatment of postoperative pain. The significant ratio and linear correlation between saliva and serum concentrations of acetaminophen suggests that saliva could be used instead of blood to monitor acetaminophen administration in patients.
authors.affiliation: Department of Pharmaceutics, The Royal Danish School of Pharmacy, Copenhagen. th@mail.dfh.dk
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
authors.initials: L
authors.lastname: Schouenborg
authors.forename: M
authors.initials: M
authors.lastname: Rasmussen
mesh_terms: D000042:Absorption; D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D012463:Saliva / Q000378:metabolism*; D013488:Suppositories
chemical_list: D018712:Analgesics, Non-Narcotic; D013488:Suppositories; D000082:Acetaminophen