Skip to main content
Journal of Medical Toxicology logoLink to Journal of Medical Toxicology
. 2010 May 6;6(3):337–344. doi: 10.1007/s13181-010-0083-9

Bactrian (“Double Hump”) Acetaminophen Pharmacokinetics: A Case Series and Review of the Literature

Robert G Hendrickson 1,2,5,, Nathanael J McKeown 1,2,3, Patrick L West 1,2, Christopher R Burke 2,4
PMCID: PMC3550480  PMID: 20446076

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.

Keywords: Acetaminophen, Toxicity, Pharmacokinetics, Bactrian, Overdose

Full Text

The Full Text of this article is available as a PDF (137.7 KB).

Footnotes

Funding

None

Previous Presentations

Presented at the North American Congress of Clinical Toxicology, San Antonio, TX, 2009.

References

  • 1.Ameer B, Divoll M, Abernethy DR, Greenblatt DJ, Shargel L. Absolute and relative bioavailability of oral acetaminophen preparations. J Pharm Sci. 1983;72(8):955–958. doi: 10.1002/jps.2600720832. [DOI] [PubMed] [Google Scholar]
  • 2.Divoll M, Abernethy DR, Ameer B, Greenblatt DJ. Acetaminophen kinetics in the elderly. Clin Pharmacol Ther. 1982;31(2):151–156. doi: 10.1038/clpt.1982.24. [DOI] [PubMed] [Google Scholar]
  • 3.Smilkstein MJ, Knapp GL, Kulig GL, et al. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. N Engl J Med. 1988;319:1557–1562. doi: 10.1056/NEJM198812153192401. [DOI] [PubMed] [Google Scholar]
  • 4.Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol. 2002;40:3–20. doi: 10.1081/clt-120002882. [DOI] [PubMed] [Google Scholar]
  • 5.Tighe TV, Walter FG. Delayed toxic acetaminophen level after initial four hour nontoxic level. Clin Toxicol. 1994;32(4):431–434. doi: 10.3109/15563659409011045. [DOI] [PubMed] [Google Scholar]
  • 6.Gesell LB, Stephan M. Delayed acetaminophen peak and toxicity in combination products [abstract] J Toxicol Clin Toxicol. 1996;34:568. [Google Scholar]
  • 7.Caraccio TR, Mofenson HC, Lawless MJ. Delayed peak acetaminophen (APAP) levels [abstract] J Toxicol Clin Toxicol. 1997;35:563. [Google Scholar]
  • 8.Ho SY, Arellano M, Zolkowski-Wynne J. Delayed increase in acetaminophen concentration after Tylenol PM overdose. Amer J Emerg Med. 1999;17(3):315–317. doi: 10.1016/s0735-6757(99)90138-9. [DOI] [PubMed] [Google Scholar]
  • 9.Spiller HA. Persistently elevated acetaminophen concentrations for two days after initial four hour non-toxic concentration. Vet Hum Toxicol. 2001;43:218–219. [PubMed] [Google Scholar]
  • 10.Bizovi KE, Aks SE, Paloucek F, et al. Late increase in acetaminophen concentration after overdose of Tylenol extended relief. Ann Emerg Med. 1996;28(5):549–551. doi: 10.1016/s0196-0644(96)70119-1. [DOI] [PubMed] [Google Scholar]
  • 11.Smith SW, Howland MA, Hoffman RS, Nelson LS. Acetaminophen overdose with altered acetaminophen pharmacokinetics and hepatotoxicity associated with premature cessation of intravenous N-acetylcysteine therapy. Ann Pharmacother. 2008;42(9):1333–1339. doi: 10.1345/aph.1K680. [DOI] [PubMed] [Google Scholar]
  • 12.Ferguson KL, Chan GM, Lee C, Greller HA, Su M. Delayed hepatotoxicity from combined acetaminophen and diphenhydramine despite 21-hour intravenous N-acetylcysteine. Clin Toxicol. 2007;45(6):6. [Google Scholar]
  • 13.Chan BS, Graudins A, Chiew A. Acetaminophen poisoning with a difference. Clin Toxicol. 2008;46(7):601–602. [Google Scholar]
  • 14.Stolbach AI, Hoffman RS, Howland MA, Nelson LS. Very late second peak in acetaminophen concentration following Tylenol extended relief overdose. Clin Toxicol. 2007;45:350. [Google Scholar]
  • 15.Schwartz EA, Hayes BD, Sarmiento KF (2008) Development of hepatic failure despite use of intravenous acetylcysteine after a massive ingestion of acetaminophen and diphenhydramine. Ann Emerg Med (article in press, November 2008) [cited May 6, 2009]; Available from http://www.annemergmed.com/inpress [DOI] [PubMed]
  • 16.Kobrinsky NL, Hartfield D, Horner H, et al. Treatment of advanced malignancies with high-dose acetaminophen and N-acetylcysteine rescue. Cancer Invest. 1996;14:202–210. doi: 10.3109/07357909609012140. [DOI] [PubMed] [Google Scholar]
  • 17.Hendrickson RG, Bizovi KE. Acetaminophen. In: Goldfrank L, Flomenbaum N, Lewin N, Howland MA, Hoffman R, Nelson L, editors. Goldfrank’s Toxicologic Emergencies. 8. Stamford: Appleton and Lange; 2006. [Google Scholar]
  • 18.Adams BK, Mann MD, Aboo A, Isaacs S, Evans A. Prolonged gastric emptying half-time and gastric hypomotility after drug overdose. Amer J Emerg Med. 2004;22(7):548–554. doi: 10.1016/j.ajem.2004.08.017. [DOI] [PubMed] [Google Scholar]
  • 19.Halcomb SE, Sivilotti MLA, Goklaney A, Mullins ME. Pharmacokinetic effects of diphenhydramine or oxycodone in simulated acetaminophen overdose. Acad Emerg Med. 2005;12(2):169–172. doi: 10.1197/j.aem.2004.10.014. [DOI] [PubMed] [Google Scholar]
  • 20.Waring WS, Benhalim S. Serum acetaminophen concentrations after acute overdose are not altered by opioid co-ingestion. J Toxicol Sci. 2008;33(5):549–553. doi: 10.2131/jts.33.549. [DOI] [PubMed] [Google Scholar]
  • 21.Hojer J, Personne M. Endoscopic removal of slow release clomipramine bezoars in two cases of acute poisoning. Clin Toxicol. 2008;46(4):317–319. doi: 10.1080/15563650701378738. [DOI] [PubMed] [Google Scholar]
  • 22.Iberti T, Patterson B, Fisher C.Prolonged bromide intoxication resulting from a gastric bezoar Arch Intern Med 1984144402–403.10.1001/archinte.144.2.402 [PubMed] [Google Scholar]
  • 23.Jenis EH, Payne RJ, Goldbaum LR. Acute meprobamate poisoning: a fatal case following a lucid interval. JAMA. 1969;207:361–365. doi: 10.1001/jama.207.2.361. [DOI] [PubMed] [Google Scholar]
  • 24.Roberts MS, Magnusson BM, Burzxynski FJ, Weiss M. Enterhepatic circulation: physiological, pharmacokinetic and clinical implications. Clin Pharmacokinet. 2002;41:751–790. doi: 10.2165/00003088-200241100-00005. [DOI] [PubMed] [Google Scholar]
  • 25.Seigers CP, Rozman K, Klaassen CD. Biliary excretion and enterohepatic circulation of paracetamol in the rat. Xenobiotica. 1983;13:591–596. doi: 10.3109/00498258309052218. [DOI] [PubMed] [Google Scholar]
  • 26.Watari N, Iwai M, Kaneniwa N. Pharmacokinetic study of the fate of acetaminophen and its conjugates in rats. J Pharmacokinet Biopharm. 1983;11:245–272. doi: 10.1007/BF01061867. [DOI] [PubMed] [Google Scholar]
  • 27.Christophersen AB, Hoegberg LCG, Kristensen K, Skanning PG, Angelo HR, Christensen HR. The effect of activated charcoal, given as an oral solution, on the elimination half-life of intravenous paracetamol. Clin Toxicol. 2004;42(4):561. [Google Scholar]
  • 28.Singer AJ, Carracio TR, Mofenson HC. The temporal profile of increased transaminase levels in patients with acetaminophen-induced liver dysfunction. Ann Emerg Med. 1995;26(1):49–53. doi: 10.1016/s0196-0644(95)70237-7. [DOI] [PubMed] [Google Scholar]
  • 29.Spiller HA, Winter ML, Klein-Schwartz W, Bangh SA. Efficacy of activated charcoal administered more than four hours after acetaminophen overdose. J Emerg Med. 2006;30(1):1–5. doi: 10.1016/j.jemermed.2005.02.019. [DOI] [PubMed] [Google Scholar]
  • 30.Olkkola KT. Effect of charcoal-drug ratio on antidotal efficacy of oral activated charcoal in man. Br J Clin Pharmac. 1985;19:767–773. doi: 10.1111/j.1365-2125.1985.tb02712.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Dart RC, Rumack BH. Patient-tailored acetylcysteine administration. Ann Emerg Med. 2007;50:280–281. doi: 10.1016/j.annemergmed.2007.01.015. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Toxicology are provided here courtesy of Springer

RESOURCES