title: Plasma concentrations after high-dose (45 mg.kg-1) rectal acetaminophen in children.
abstract: Although the recommended dose of rectal acetaminophen (25-30 mg.kg-1) is twice that for oral administration (10-15 mg.kg-1), the literature justifies the use of a higher dose when acetaminophen is administered via the rectal route. We measured venous plasma acetaminophen concentrations resulting from 45 mg.kg-1 of rectal acetaminophen in ten ASA 1, 15 kg paediatric patients undergoing minor surgery with a standardized anaesthetic. After induction of anaesthesia, a single 650 mg suppository (Abenol, SmithKline Beecham Pharma Inc.) was administered rectally. Plasma was sampled at t = 0, 15, 30, 45, 60, 90, 120, 180, 240 min in the first five patients and at t = 0, 30, 60, 90, 120, 180, 240, 300, 420 min in the subsequent five. Acetaminophen plasma concentrations were determined using a TDxFLx fluorescence polarization immunoassay (Abbott Laboratories, Toronto, Ontario). The maximum plasma concentration was 88 +/- 39 mumol.L-1 (13 +/- 6 micrograms.ml-1) and the time of peak plasma concentration was 198 +/- 70 min (mean +/- SD). At 420 min, the mean plasma concentration was 46 +/- 18 mumol.L-1 (7.0 +/- 0.9 micrograms.ml-1). No plasma concentrations associated with toxicity (> 800 mumol.L-1) were identified. A 45 mg.kg-1 rectal dose of acetaminophen resulted in peak plasma concentrations comparable with those resulting from 10-15 mg.kg-1 of oral acetaminophen at three hours after suppository insertion. It is concluded that the delayed and erratic absorption of acetaminophen after rectal administration leads to unpredictable plasma concentrations. Rectal acetaminophen will not be consistently effective for providing rapid onset of analgesia in children.
authors.affiliation: Department of Anaesthesia, University of British Columbia, Vancouver, Canada.
authors.forename: C J
authors.initials: CJ
authors.lastname: Montgomery
authors.forename: J P
authors.initials: JP
authors.lastname: McCormack
authors.forename: C C
authors.initials: CC
authors.lastname: Reichert
authors.forename: C P
authors.initials: CP
authors.lastname: Marsland
mesh_terms: D000042:Absorption; D000082:Acetaminophen / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000285:Administration, Rectal; D000698:Analgesia; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D000768:Anesthesia, General; D002648:Child; D002675:Child, Preschool; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D008297:Male; D013511:Minor Surgical Procedures; D011446:Prospective Studies; D013488:Suppositories; D013997:Time Factors
chemical_list: D018712:Analgesics, Non-Narcotic; D013488:Suppositories; D000082:Acetaminophen