Abstract
Generation of protein-derived acetaminophen-cysteine (APAP-CYS) is reported after ingestion of large and therapeutic dosages of acetaminophen in healthy and in liver-damaged patients. The incidence of protein-derived APAP-CYS adducts in repeated supratherapeutic dosages of APAP is not known. Methods: for 12 months, a standardized and comprehensive questionnaire was used to interview every consecutive patient at a pain management clinic. Patients found to ingest more than 4 g of APAP per day for a minimum of 14 consecutive days at the time of the encounter were invited to have blood drawn for hepatic transaminases and APAP-CYS adduct levels. Twelve subjects out of 990 interviewees met inclusion criteria. Ten of the 12 had measurable protein-derived APAP-CYS, none had evidence of liver injury. Patients that ingest repeated supratherapeutic amounts of APAP over several weeks may generate APAP-CYS protein adducts in the absence of hepatic injury.
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References
McGill MR, Lebofsky M, Norris HYK, et al. Plasma and liver acetaminophen-protein adduct levels in mice after acetaminophen treatment: dose-response, mechanisms and clinical implications. Toxicol Appl Pharmacol. 2013;269(3):240–9.
Heard KJ, Green JL, James LP, Judge BS, Zolot L, Rhyee S, et al. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose. BMC Gastroenterol. 2011;14:11–20.
Curry SC, Padilla-Jones A, O’Connor AD, Ruha AM, Bikin DS, Wilkins DG, et al. Prolonged acetaminophen-protein adduct elimination during renal failure, lack of adduct removal by hemodiafiltration, and urinary adduct concentrations after acetaminophen overdose. JMT. 2014. doi:10.1007/s13181-014-0431-2.
Bond GR. Acetaminophen protein adducts: a review. Clin Toxicol. 2009;47(1):2–7.
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, et al. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos. 2009;37(8):1779–84.
James LP, Chiew A, Abdel-Rahman SM, Letzig L, Graudins A, Day P, et al. Acetaminophen protein adduct formation following low dose acetaminophen exposure: comparison of immediate-release vs extended-release formulation. Eur J Clin Pharmacol. 2013;69(4):851–7.
Khandelwal N, James LP, Sanders C, Larson AM, Lee WM, Acute Liver Failure Study Group. Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure. Hepatology. 2011;53(2):567–76.
James LP, Alonso EM, Hynan LS, Hinson JA, Davern TJ, Lee WM, et al. Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. Pediatrics. 2006;118(3):676–81.
Cook SF, King AD, Chang Y, Murray GJ, Norris HR, Dart RC, et al. Quantification of a biomarker of acetaminophen protein adducts in human serum by high-performance liquid chromatography-electrospray ionization-tandem mass spectroscopy: clinical and animal model applications. J Chromatogr B Analyt Technol Biomed Life Sci. 2015;985:131–41.
Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42(6):1364–72.
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The manuscript was made possible through a generous unrestricted educational grant from McNeil Pharmaceuticals.
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O’Malley, G., Mizrahi, F., Giraldo, P. et al. Protein-Derived Acetaminophen-Cysteine Can Be Detected After Repeated Supratherapeutic Ingestion of Acetaminophen in the Absence of Hepatotoxicity. J. Med. Toxicol. 11, 317–320 (2015). https://doi.org/10.1007/s13181-015-0484-x
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DOI: https://doi.org/10.1007/s13181-015-0484-x