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dc.contributor.authorHeard, Kennon J.
dc.contributor.authorGreen, Jody L.
dc.contributor.authorJames, Laura P.
dc.contributor.authorJudge, Bryan S.
dc.contributor.authorZolot, Liza
dc.contributor.authorRhyee, Sean Hyun
dc.contributor.authorDart, Richard C.
dc.date2022-08-11T08:09:40.000
dc.date.accessioned2022-08-23T16:39:22Z
dc.date.available2022-08-23T16:39:22Z
dc.date.issued2011-03-14
dc.date.submitted2012-03-22
dc.identifier.citationBMC Gastroenterol. 2011 Mar 14;11:20. <a href="http://dx.doi.org/10.1186/1471-230X-11-20" target="_blank">Link to article on publisher's site</a>
dc.identifier.issn1471-230X (Linking)
dc.identifier.doi10.1186/1471-230X-11-20
dc.identifier.pmid21401949
dc.identifier.pmid21401949
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39458
dc.description.abstractBACKGROUND: Acetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. METHODS: Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. RESULTS: Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin. CONCLUSIONS: Lower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21401949&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1186/1471-230X-11-20
dc.rights© 2011 Heard et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.subjectAcetaminophen
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAlcohol Drinking
dc.subjectAlcoholism
dc.subjectBiological Markers
dc.subjectChild
dc.subjectCysteine
dc.subjectDose-Response Relationship, Drug
dc.subjectDrug-Induced Liver Injury
dc.subjectFemale
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectOverdose
dc.subjectYoung Adult
dc.subjectLife Sciences
dc.subjectMedical Toxicology
dc.subjectMedicine and Health Sciences
dc.titleAcetaminophen-cysteine adducts during therapeutic dosing and following overdose
dc.typeJournal Article
dc.source.journaltitleBMC gastroenterology
dc.source.volume11
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3254&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2255
dc.identifier.contextkey2691092
refterms.dateFOA2022-08-23T16:39:22Z
html.description.abstract<p>BACKGROUND: Acetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose.</p> <p>METHODS: Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection.</p> <p>RESULTS: Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin.</p> <p>CONCLUSIONS: Lower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.</p>
dc.identifier.submissionpathoapubs/2255
dc.contributor.departmentDepartment of Emergency Medicine
dc.source.pages20


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