title: Bactrian ("double hump") acetaminophen pharmacokinetics: a case series and review of the literature.
abstract: After acute ingestion, acetaminophen (APAP) is generally absorbed within 4 h and the APAP concentration ([APAP]) slowly decreases with a predictable half-life. Alterations in these pharmacokinetic principles have been rarely reported. We report here three cases of an unusual double hump, or Bactrian, pattern of [APAP]. We review the literature to describe the case characteristics of these rare cases. A 38-year-old woman ingested 2 g hydrocodone/65 g acetaminophen. Her [APAP] peaked at 289 mcg/mL (8 h), decreased to 167 mcg/mL (31 h), then increased to 240 mcg/mL (39 h). She developed liver injury (peak AST 1603 IU/L; INR1.6). A 25-year-old man ingested 2 g diphenhydramine/26 g APAP. His [APAP] peaked at 211 mcg/mL (15 h), decreased to 185 mcg/mL (20 h), and increased again to 313 mcg/mL (37 h). He developed liver injury (peak AST 1153; INR 2.1). A 16-year-old boy ingested 5 g diphenhydramine and 100 g APAP. His [APAP] peaked at 470 mcg/mL (25 h), decreased to 313 mcg/mL (36 h), then increased to 354 mcg/mL (42 h). He developed liver injury (peak AST 8,686 IU/L; peak INR 5.9). We report three cases of Bactrian ("double hump") pharmacokinetics after massive APAP overdoses. Cases with double hump pharmacokinetics may be associated with large ingestions (26-100 g APAP) and are often coingested with antimuscarinics or opioids. Several factors may contribute to these altered kinetics including the insolubility of acetaminophen, APAP-induced delays in gastric emptying, opioid or antimuscarinic effects, or enterohepatic circulation. Patients with double hump APAP concentrations may be at risk for liver injury, with AST elevations and peaks occurring later than what is typical for acute APAP overdoses.
authors.affiliation: Oregon Poison Center, Portland, OR 97210, USA. hendriro@ohsu.edu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hendrickson
authors.forename: Nathanael J
authors.initials: NJ
authors.lastname: McKeown
authors.forename: Patrick L
authors.initials: PL
authors.lastname: West
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Burke
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics* / Q000506:poisoning; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen
references.citation: Ann Emerg Med. 1996 Nov;28(5):549-51
references.pmid: 8909277
references.citation: Ann Emerg Med. 2007 Sep;50(3):280-1
references.pmid: 17418449
references.citation: JAMA. 1969 Jan 13;207(2):361-2
references.pmid: 5818163
references.citation: Clin Pharmacokinet. 2002;41(10):751-90
references.pmid: 12162761
references.citation: Clin Pharmacol Ther. 1982 Feb;31(2):151-6
references.pmid: 7056022
references.citation: Am J Emerg Med. 2004 Nov;22(7):548-54
references.pmid: 15666259
references.citation: Acad Emerg Med. 2005 Feb;12(2):169-72
references.pmid: 15692141
references.citation: J Toxicol Clin Toxicol. 2002;40(1):3-20
references.pmid: 11990202
references.citation: Cancer Invest. 1996;14(3):202-10
references.pmid: 8630680
references.citation: Br J Clin Pharmacol. 1985 Jun;19(6):767-73
references.pmid: 4027120
references.citation: J Emerg Med. 2006 Jan;30(1):1-5
references.pmid: 16434328
references.citation: Vet Hum Toxicol. 2001 Aug;43(4):218-9
references.pmid: 11474737
references.citation: J Toxicol Clin Toxicol. 1994;32(4):431-4
references.pmid: 7914547
references.citation: Ann Emerg Med. 2009 Sep;54(3):421-3
references.pmid: 18986731
references.citation: Am J Emerg Med. 1999 May;17(3):315-7
references.pmid: 10337903
references.citation: J Toxicol Sci. 2008 Dec;33(5):549-53
references.pmid: 19043276
references.citation: Ann Emerg Med. 1995 Jul;26(1):49-53
references.pmid: 7793720
references.citation: Clin Toxicol (Phila). 2008 Apr;46(4):317-9
references.pmid: 18363128
references.citation: J Pharm Sci. 1983 Aug;72(8):955-8
references.pmid: 6688635
references.citation: Ann Pharmacother. 2008 Sep;42(9):1333-9
references.pmid: 18628444
references.citation: J Pharmacokinet Biopharm. 1983 Jun;11(3):245-72
references.pmid: 6644552
references.citation: Arch Intern Med. 1984 Feb;144(2):402-3
references.pmid: 6696579
references.citation: N Engl J Med. 1988 Dec 15;319(24):1557-62
references.pmid: 3059186
references.citation: Xenobiotica. 1983 Oct;13(10):591-6
references.pmid: 6673372