Terbinafine由於有效且耐受性佳,目前是皮膚學界公認為治療皮癬菌甲癬的首選藥物。使用terbinafine偶會造成肝臟受損,但是其肝毒性機轉仍不清楚。本研究使用大白鼠給與Terbinafine 4mg/kg/day的臨床治療劑量,以探討肝臟的病理變化。在給與terbinafine二至六週的大白鼠,其血液與生化檢查均為正常(除了alkaline phosphotase在二週時暫時升高外),組織病理在六週時方顯現脂肪病變;電子顯微鏡檢查,二週時的肝細胞只有些許的脂肪滴,但是六週時的肝細胞則富含脂肪滴,并有高電子密度不定形物存在於肝細胞內。肝細胞與微小膽管也有膽汁滯留,此外,較為特殊的是發現肝細胞內出現含有針狀物質似phagosome的胞器。本動物實驗顯示臨床治療劑量使用的terbinafine,對大白鼠可能有肝臟的毒性,相較於生化與組織學檢查,電子顯微鏡用以偵測肝臟病變是更為敏感的工具。
Terbinafine has been suggested as the treatment of choice for dermatophyte onychomycosis, and has excellent tolerability in treated patients. Hepatic injury has been reported with the use of terbinafine, however, the mechanism of hepatotoxicity is still obscure. The present study was designed to investigate the pathology of the liver in rats following administration of the therapeutic dose of terbinafine 4mg/kg b.w. p.o., daily. The hemogram and biochemistry including liver enzymes were all normal in all groups of rats following treatment, except for a transient increase in the level of alkaline phosphatase in rats treated with terbinafine after 2 weeks. The histology of the liver revealed fatty change in terbinafine-treated rats at 6 weeks. Ultrastructurally, only a few lipid droplets in occasional hepatocytes were found at 2 weeks. However, abundant lipid droplets with deposition of amorphous electron-dense substances were found in hepatocytes in rats treated for 6 weeks. Bile was found in the hepatocytes and in bile duct canaliculi. Moreover, the unique finding of a phagosome-like structure containing needle- shape substance was observed in hepatocytes. In conclusion, we demonstrated that terbinafine in therapeutic doses may have hepatotoxicity in rats. In comparison with liver enzyme tests and histological examination, electron microscopy is a more sensitive tool to detect the liver pathology.
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