Acetaminophen-cysteine adducts during therapeutic dosing and following overdose
<p>Abstract</p> <p>Background</p> <p>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 m...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-03-01
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| Series: | BMC Gastroenterology |
| Online Access: | http://www.biomedcentral.com/1471-230X/11/20 |
| _version_ | 1818641785804554240 |
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| author | Judge Bryan S James Laura P Green Jody L Heard Kennon J Zolot Liza Rhyee Sean Dart Richard C |
| author_facet | Judge Bryan S James Laura P Green Jody L Heard Kennon J Zolot Liza Rhyee Sean Dart Richard C |
| author_sort | Judge Bryan S |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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</p> <p>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</p> <p>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</p> <p>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> |
| first_indexed | 2024-12-16T23:32:41Z |
| format | Article |
| id | doaj.art-0492fbf07f52433ea9464add69e92513 |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-12-16T23:32:41Z |
| publishDate | 2011-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-0492fbf07f52433ea9464add69e925132022-12-21T22:11:48ZengBMCBMC Gastroenterology1471-230X2011-03-011112010.1186/1471-230X-11-20Acetaminophen-cysteine adducts during therapeutic dosing and following overdoseJudge Bryan SJames Laura PGreen Jody LHeard Kennon JZolot LizaRhyee SeanDart Richard C<p>Abstract</p> <p>Background</p> <p>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</p> <p>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</p> <p>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</p> <p>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>http://www.biomedcentral.com/1471-230X/11/20 |
| spellingShingle | Judge Bryan S James Laura P Green Jody L Heard Kennon J Zolot Liza Rhyee Sean Dart Richard C Acetaminophen-cysteine adducts during therapeutic dosing and following overdose BMC Gastroenterology |
| title | Acetaminophen-cysteine adducts during therapeutic dosing and following overdose |
| title_full | Acetaminophen-cysteine adducts during therapeutic dosing and following overdose |
| title_fullStr | Acetaminophen-cysteine adducts during therapeutic dosing and following overdose |
| title_full_unstemmed | Acetaminophen-cysteine adducts during therapeutic dosing and following overdose |
| title_short | Acetaminophen-cysteine adducts during therapeutic dosing and following overdose |
| title_sort | acetaminophen cysteine adducts during therapeutic dosing and following overdose |
| url | http://www.biomedcentral.com/1471-230X/11/20 |
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