title: Lack of hepato- and nephrotoxicity induced by antifungal drug voriconazole in laboratory rats.
abstract: Voriconazole is a new, potent broad-spectrum triazole systemic antifungal drug, a second-generation azole antifungal that is increasing in popularity, especially for the treatment of invasive aspergillosis and fluconazole-resistant invasive Candida infections. However, it is also known to induce hepatotoxicity clinically. The aim of this study was to investigate the hepatotoxicity and nephrotoxicity potential of voriconazole in vivo in rats. Forty rats were treated intraperitoneally with voriconazole as single (0, 10, l00, and 200 mg/kg) or repeated (0, 10, 50, and l00 mg/kg per day for 14 days) doses. Venous blood was collected for the repeated-dose group on days 1 and 14. Rats were sacrificed 24 hours after the last dose. Body weight, liver weight, and kidney weight of rats were recorded. Livers and kidneys samples were taken for histological and transmission electron microscopy (TEM) analysis. Results revealed that voriconazole had no effects on serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphotase, gamma glutamyl transpeptidase, blood urea nitrogen, and creatinine for both the single- and repeated-dose groups. However, histologically, in the repeated 50- and 100-mg/kg voriconazole-treated rats, mild focal inflammation was observed. Under TEM, only small changes in the 100 mg/kg/day group were revealed. These results collectively demonstrated that voriconazole did not induce significant hepatotoxicity and nephrotoxicity, even at very high doses.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Serdang, Malaysia. nhareet@medic.upm.edu.my
authors.forename: Nhareet
authors.initials: N
authors.lastname: Somchit
authors.forename: Jun Hung
authors.initials: JH
authors.lastname: Chung
authors.forename: Azhar
authors.initials: A
authors.lastname: Yaacob
authors.forename: Zuraini
authors.initials: Z
authors.lastname: Ahmad
authors.forename: Zainul A
authors.initials: ZA
authors.lastname: Zakaria
authors.forename: Arifah A
authors.initials: AA
authors.lastname: Kadir
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests / Q000379:methods; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D065819:Voriconazole; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D065819:Voriconazole