High‐dose rectal and oral acetaminophen in postoperative patients – serum and saliva concentrations

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 μmol/l, 33.7±12.5 μmol/l, 45.5±19.1 μmol/l, and 55.4±23.1 μmol/l, respectively. The serum concentrations at 2 and 4 h were 31.0±11.2 μmol/l and 54.8±23.8 μmol/l, respectively. Additional oral dosing resulted in saliva concentrations at 5, 8, and 9 h of 99.7±49.5 μmol/l, 106.9±31.7 μmol/l, and 139.3±55.4 μmol/l, respectively, with coincident serum concentrations of 100.1±50.2 μmol/l, 105.6±29.0 μmol/l, and 141.2±52.1 μmol/l. After rectal dosing the linear regression resulted in r 2 =0.96, P <0.001 and saliva/serum‐ratio=0.99. After additional oral dosing the outcome of linear regression was: r 2 =0.90, P <0.001 and saliva/serum‐ratio=1.00. Conclusion: 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.