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Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study

Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely un...

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Main Authors: Abdullah, Muhammad Nazrul Hakim, Abdul Rahman, Nor Shahida, Ab. Hamid, Hasiah, Ahmad, Zuraini, Sulaiman, Mohd Roslan, Mohamed Mustapha, Noordin
Format: Article
Language:English
Published: SAGE Publications 2004
Online Access:http://psasir.upm.edu.my/id/eprint/18555/1/Hepatotoxicity%20induced%20by%20antifungal%20drugs%20itraconazole%20and%20fluconazole%20in%20rats.pdf
http://psasir.upm.edu.my/id/eprint/18555/
http://het.sagepub.com/content/23/11/519
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spelling my.upm.eprints.185552016-09-01T05:28:55Z http://psasir.upm.edu.my/id/eprint/18555/ Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study Abdullah, Muhammad Nazrul Hakim Abdul Rahman, Nor Shahida Ab. Hamid, Hasiah Ahmad, Zuraini Sulaiman, Mohd Roslan Mohamed Mustapha, Noordin Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, 100 and 200 mg/kg) or subchronic (0, 10, 50 and 100 mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase [ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granulome were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats. SAGE Publications 2004-11 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/18555/1/Hepatotoxicity%20induced%20by%20antifungal%20drugs%20itraconazole%20and%20fluconazole%20in%20rats.pdf Abdullah, Muhammad Nazrul Hakim and Abdul Rahman, Nor Shahida and Ab. Hamid, Hasiah and Ahmad, Zuraini and Sulaiman, Mohd Roslan and Mohamed Mustapha, Noordin (2004) Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study. Human & Experimental Toxicology, 23 (11). pp. 519-525. ISSN 0960-3271; ESSN: 1477-0903 http://het.sagepub.com/content/23/11/519 doi:10.1191/0960327104ht479oa
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, 100 and 200 mg/kg) or subchronic (0, 10, 50 and 100 mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase [ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granulome were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats.
format Article
author Abdullah, Muhammad Nazrul Hakim
Abdul Rahman, Nor Shahida
Ab. Hamid, Hasiah
Ahmad, Zuraini
Sulaiman, Mohd Roslan
Mohamed Mustapha, Noordin
spellingShingle Abdullah, Muhammad Nazrul Hakim
Abdul Rahman, Nor Shahida
Ab. Hamid, Hasiah
Ahmad, Zuraini
Sulaiman, Mohd Roslan
Mohamed Mustapha, Noordin
Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study
author_facet Abdullah, Muhammad Nazrul Hakim
Abdul Rahman, Nor Shahida
Ab. Hamid, Hasiah
Ahmad, Zuraini
Sulaiman, Mohd Roslan
Mohamed Mustapha, Noordin
author_sort Abdullah, Muhammad Nazrul Hakim
title Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study
title_short Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study
title_full Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study
title_fullStr Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study
title_full_unstemmed Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study
title_sort hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study
publisher SAGE Publications
publishDate 2004
url http://psasir.upm.edu.my/id/eprint/18555/1/Hepatotoxicity%20induced%20by%20antifungal%20drugs%20itraconazole%20and%20fluconazole%20in%20rats.pdf
http://psasir.upm.edu.my/id/eprint/18555/
http://het.sagepub.com/content/23/11/519
_version_ 1643826834211602432
score 13.211869

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