Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical Trial
Background: N-acetylcysteine (NAC) has been used as a classic treatment for hepatotoxicity induced by N- acetyl-p-benzoquinone imine (NAPQI) as a metabolite of acetaminophen. However, cimetidine theoretically can reduce the production of toxic metabolites through the inhibition of cytochrome p450,...
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| Format: | Article |
| Language: | English |
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Electronic Physician
2015-10-01
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| Series: | Electronic Physician |
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623788/ |
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| author | Mohsen Ebrahimi Seyed Reza Mousavi Alireza Ghassemi Toussi Hamidreza Reihani Farhad Bagherian |
| author_facet | Mohsen Ebrahimi Seyed Reza Mousavi Alireza Ghassemi Toussi Hamidreza Reihani Farhad Bagherian |
| author_sort | Mohsen Ebrahimi |
| collection | DOAJ |
| description | Background: N-acetylcysteine (NAC) has been used as a classic treatment for hepatotoxicity induced by N- acetyl-p-benzoquinone imine (NAPQI) as a metabolite of acetaminophen. However, cimetidine theoretically can
reduce the production of toxic metabolites through the inhibition of cytochrome p450, and it recently was
proposed as a complementary treatment for acetaminophen toxicity.
Objective: The aim of this study was to compare the effects of treating acute acetaminophen toxicity with NAC
alone and with a combination of NAC and cimetidine.
Methods: From October 2013 to March 2014, 105 patients suspected of acetaminophen toxicity who had
paraclinical confirmation of toxicity requiring medical treatment (based on the risk assessment nomogram of
acetaminophen serum level) were enrolled in this double-blind, randomized, controlled trial at Imam Reza
Hospital in Mashhad, Iran. The patients were divided into two groups, i.e., 1) patients who were treated with
NAC alone (group A) and 2) patients who were treated with a combination of NAC and cimetidine (group B).
The primary outcomes were 1) the serum level of acetaminophen and 2) the serum level of aminotransferases at
the time of admission and 4, 12, 24, and 48 hours after admission. Exclusion criteria included multiple toxicities,
concurrent diseases that could affect liver enzymes, the use of other drugs, and dissatisfaction with the project.
For measuring quantitative data, SPSS version 16 was used for t-test analysis and for analyzing the qualitative
data with chi-squared analysis.
Results: Sixty patients (32 females and 28 males) with a mean age of 25.2 ± 7.3 years were classified in two
groups of 30.. There was no difference between the groups in terms of their admission information. The average
levels of acetaminophen in both groups at admission, 12, 24, and 48 hours after hospitalization were not
significantly different from each other. Twelve hours after hospitalization, the aspartate aminotransferase (AST)
level in the group treated with NAC was significantly higher than in the group treated with the combination of
NAC and cimetidine (IU/L30.1 ± 110.0 versus IU/L26.38 ± 94.93, p = 0.044). At the other times that the level of
liver enzymes was assessed, the serum levels of urea and creatinine were not significantly different in the two
groups (p > 0.05)
Conclusion: The intravenous administration of 300 mg of cimetidine every six hours with NAC did not improve
the level of hepatoprotective action significantly compared with the NAC treatment protocol alone.
Trial registration: The trial was registered at the Iranian Clinical Trial Registry (IRCT.ir) with the IRCT
identification number IRCT2013102915204N1.
Funding: This research was supported financially by the Research Council of Mashhad University of Medical
Sciences (Grant Number: 920427). |
| first_indexed | 2024-12-13T19:04:11Z |
| format | Article |
| id | doaj.art-6cf789be9c094df6b38073b9887bb085 |
| institution | Directory Open Access Journal |
| issn | 2008-5842 2008-5842 |
| language | English |
| last_indexed | 2024-12-13T19:04:11Z |
| publishDate | 2015-10-01 |
| publisher | Electronic Physician |
| record_format | Article |
| series | Electronic Physician |
| spelling | doaj.art-6cf789be9c094df6b38073b9887bb0852022-12-21T23:34:37ZengElectronic PhysicianElectronic Physician2008-58422008-58422015-10-01761310131710.14661/1310Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical TrialMohsen EbrahimiSeyed Reza MousaviAlireza Ghassemi ToussiHamidreza ReihaniFarhad BagherianBackground: N-acetylcysteine (NAC) has been used as a classic treatment for hepatotoxicity induced by N- acetyl-p-benzoquinone imine (NAPQI) as a metabolite of acetaminophen. However, cimetidine theoretically can reduce the production of toxic metabolites through the inhibition of cytochrome p450, and it recently was proposed as a complementary treatment for acetaminophen toxicity. Objective: The aim of this study was to compare the effects of treating acute acetaminophen toxicity with NAC alone and with a combination of NAC and cimetidine. Methods: From October 2013 to March 2014, 105 patients suspected of acetaminophen toxicity who had paraclinical confirmation of toxicity requiring medical treatment (based on the risk assessment nomogram of acetaminophen serum level) were enrolled in this double-blind, randomized, controlled trial at Imam Reza Hospital in Mashhad, Iran. The patients were divided into two groups, i.e., 1) patients who were treated with NAC alone (group A) and 2) patients who were treated with a combination of NAC and cimetidine (group B). The primary outcomes were 1) the serum level of acetaminophen and 2) the serum level of aminotransferases at the time of admission and 4, 12, 24, and 48 hours after admission. Exclusion criteria included multiple toxicities, concurrent diseases that could affect liver enzymes, the use of other drugs, and dissatisfaction with the project. For measuring quantitative data, SPSS version 16 was used for t-test analysis and for analyzing the qualitative data with chi-squared analysis. Results: Sixty patients (32 females and 28 males) with a mean age of 25.2 ± 7.3 years were classified in two groups of 30.. There was no difference between the groups in terms of their admission information. The average levels of acetaminophen in both groups at admission, 12, 24, and 48 hours after hospitalization were not significantly different from each other. Twelve hours after hospitalization, the aspartate aminotransferase (AST) level in the group treated with NAC was significantly higher than in the group treated with the combination of NAC and cimetidine (IU/L30.1 ± 110.0 versus IU/L26.38 ± 94.93, p = 0.044). At the other times that the level of liver enzymes was assessed, the serum levels of urea and creatinine were not significantly different in the two groups (p > 0.05) Conclusion: The intravenous administration of 300 mg of cimetidine every six hours with NAC did not improve the level of hepatoprotective action significantly compared with the NAC treatment protocol alone. Trial registration: The trial was registered at the Iranian Clinical Trial Registry (IRCT.ir) with the IRCT identification number IRCT2013102915204N1. Funding: This research was supported financially by the Research Council of Mashhad University of Medical Sciences (Grant Number: 920427).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623788/acetaminophenacetylcysteinecimetidine |
| spellingShingle | Mohsen Ebrahimi Seyed Reza Mousavi Alireza Ghassemi Toussi Hamidreza Reihani Farhad Bagherian Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical Trial Electronic Physician acetaminophen acetylcysteine cimetidine |
| title | Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical Trial |
| title_full | Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical Trial |
| title_fullStr | Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical Trial |
| title_full_unstemmed | Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical Trial |
| title_short | Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical Trial |
| title_sort | comparing the therapeutic effectiveness of n acetylcysteine with the combination of n acetyl cysteine and cimetidine in acute acetaminophen toxicity a double blinded clinical trial |
| topic | acetaminophen acetylcysteine cimetidine |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623788/ |
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