Acetaminophen-cysteine adducts during therapeutic dosing and following overdose
dc.contributor.author | Heard, Kennon J. | |
dc.contributor.author | Green, Jody L. | |
dc.contributor.author | James, Laura P. | |
dc.contributor.author | Judge, Bryan S. | |
dc.contributor.author | Zolot, Liza | |
dc.contributor.author | Rhyee, Sean Hyun | |
dc.contributor.author | Dart, Richard C. | |
dc.date | 2022-08-11T08:09:40.000 | |
dc.date.accessioned | 2022-08-23T16:39:22Z | |
dc.date.available | 2022-08-23T16:39:22Z | |
dc.date.issued | 2011-03-14 | |
dc.date.submitted | 2012-03-22 | |
dc.identifier.citation | BMC 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.issn | 1471-230X (Linking) | |
dc.identifier.doi | 10.1186/1471-230X-11-20 | |
dc.identifier.pmid | 21401949 | |
dc.identifier.pmid | 21401949 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/39458 | |
dc.description.abstract | 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. 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.iso | en_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.url | http://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.subject | Acetaminophen | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Alcohol Drinking | |
dc.subject | Alcoholism | |
dc.subject | Biological Markers | |
dc.subject | Child | |
dc.subject | Cysteine | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Drug-Induced Liver Injury | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Middle Aged | |
dc.subject | Overdose | |
dc.subject | Young Adult | |
dc.subject | Life Sciences | |
dc.subject | Medical Toxicology | |
dc.subject | Medicine and Health Sciences | |
dc.title | Acetaminophen-cysteine adducts during therapeutic dosing and following overdose | |
dc.type | Journal Article | |
dc.source.journaltitle | BMC gastroenterology | |
dc.source.volume | 11 | |
dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3254&context=oapubs&unstamped=1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/oapubs/2255 | |
dc.identifier.contextkey | 2691092 | |
refterms.dateFOA | 2022-08-23T16:39:22Z | |
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.submissionpath | oapubs/2255 | |
dc.contributor.department | Department of Emergency Medicine | |
dc.source.pages | 20 |