Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats
Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity indu...
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| Format: | Article |
| Jezik: | English |
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Hindawi Limited
2017-01-01
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| Serija: | Journal of Toxicology |
| Online dostop: | http://dx.doi.org/10.1155/2017/6746989 |
| _version_ | 1827088147318571008 |
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| author | Star Khoza Ishmael Moyo Denver Ncube |
| author_facet | Star Khoza Ishmael Moyo Denver Ncube |
| author_sort | Star Khoza |
| collection | DOAJ |
| description | Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p=0.0017) and AST levels (p=0.0008) than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (p<0.0001). The liver enzyme levels suggested that ketoconazole had the highest risk in causing liver injury followed by itraconazole, fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination. |
| first_indexed | 2025-03-20T05:03:59Z |
| format | Article |
| id | doaj.art-6723838544a843b785e901b8ed3a0612 |
| institution | Directory Open Access Journal |
| issn | 1687-8191 1687-8205 |
| language | English |
| last_indexed | 2025-03-20T05:03:59Z |
| publishDate | 2017-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj.art-6723838544a843b785e901b8ed3a06122024-10-03T05:36:30ZengHindawi LimitedJournal of Toxicology1687-81911687-82052017-01-01201710.1155/2017/67469896746989Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in RatsStar Khoza0Ishmael Moyo1Denver Ncube2Department of Clinical Pharmacology, College of Health Sciences, University of Zimbabwe, Harare, ZimbabweDepartment of Clinical Pharmacology, College of Health Sciences, University of Zimbabwe, Harare, ZimbabweDepartment of Anatomy, College of Health Sciences, University of Zimbabwe, Harare, ZimbabweOral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p=0.0017) and AST levels (p=0.0008) than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (p<0.0001). The liver enzyme levels suggested that ketoconazole had the highest risk in causing liver injury followed by itraconazole, fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.http://dx.doi.org/10.1155/2017/6746989 |
| spellingShingle | Star Khoza Ishmael Moyo Denver Ncube Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats Journal of Toxicology |
| title | Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats |
| title_full | Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats |
| title_fullStr | Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats |
| title_full_unstemmed | Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats |
| title_short | Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats |
| title_sort | comparative hepatotoxicity of fluconazole ketoconazole itraconazole terbinafine and griseofulvin in rats |
| url | http://dx.doi.org/10.1155/2017/6746989 |
| work_keys_str_mv | AT starkhoza comparativehepatotoxicityoffluconazoleketoconazoleitraconazoleterbinafineandgriseofulvininrats AT ishmaelmoyo comparativehepatotoxicityoffluconazoleketoconazoleitraconazoleterbinafineandgriseofulvininrats AT denverncube comparativehepatotoxicityoffluconazoleketoconazoleitraconazoleterbinafineandgriseofulvininrats |