Terbinafine (TDT 067) is a novel allylamine antifungal agent and a potent noncompetitive squalene cyclooxygenase inhibitor (Ki value is 30 nM) that selectively inhibits squalene cyclooxygenase, leading to a decrease in ergosterol, which interferes with membrane function and cell growth[1-2].
Terbinafine stimulates ROS production in HaCaT cells and induces a HaCaT Cytotoxic response with IC50 values of 12.5-25 μg/mL, and the Terbinafine group exhibited moderate cell rounding and cell shrinkage compared to untreated control and vector control[3]. Terbinafine (0, 30, 60 and 120 μM) concentration-dependently increased the activity of the p21 promoter in HUVEC and induced HUVEC cell cycle arrest by upregulating the p21 protein[4].
Terbinafine showed good antifungal activity against cutaneous fungal disease in guinea pigs caused by Trichophyton mentagrophytes or Microsporum canis[5]. After oral administration of Terbinafine at a dose of 30 mg/kg, the maximum plasma levels in cats, greyhounds and red-tailed eagles were 3.22, 4.01 and 1.2 μg/ml, respectively. The differences in the half-life of Terbinafine were not significant in cats (8.01 h), greyhounds (8.6 h), and horses (8.1 h), whereas it was significantly prolonged in the red-tailed eagles (17.5 h) and the African penguins ( 17.0 h) were significantly prolonged[2].
References:
[1]. Ryder NS, et al. Terbinafine: mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol. 1992 Feb;126 Suppl 39:2-7.
[2]. Wang A, Ding H, Liu Y, et al. Single dose pharmacokinetics of terbinafine in cats[J]. Journal of feline medicine and surgery, 2012, 14(8): 540-544.
[3]. Lam P L, Wong M M, Hung L K, et al. Miconazole and terbinafine induced reactive oxygen species accumulation and topical toxicity in human keratinocytes[J]. Drug and Chemical Toxicology, 2022, 45(2): 834-838.
[4]. Ho PY, Hsu SP, Liang YC, Kuo ML, Ho YS, Lee WS. Inhibition of the ERK phosphorylation plays a role in terbinafine-induced p21 up-regulation and DNA synthesis inhibition in human vascular endothelial cells. Toxicol Appl Pharmacol. 2008 May 15;229(1):86-93.
[5]. Petranyi G, Meingassner JG, Mieth H. Activity of terbinafine in experimental fungal infections of laboratory animals. Antimicrob Agents Chemother. 1987 Oct;31(10):1558-61.
Terbinafine（TDT 067）是一种新型烯丙胺类抗真菌剂，也是一种有效的非竞争性角鲨烯环氧化酶抑制剂（Ki值为30 nM），可以选择性地抑制角鲨烯环氧化酶，导致麦角甾醇的减少，从而干扰膜功能和细胞生长[1-2]。
Terbinafine可刺激HaCaT细胞中ROS的产生，诱导HaCaT细胞毒性反应，IC50值为12.5-25 μg/mL，与未处理的对照和载体对照相比，Terbinafine组表现出中等程度的细胞圆化和细胞收缩[3]。Terbinafine（0、30、60和120 μM）浓度依赖性地增加了HUVEC中p21启动子的活性，并通过上调p21蛋白诱导HUVEC细胞周期停滞[4]。
Terbinafine对毛癣菌或犬小孢子菌引起的豚鼠皮肤真菌病显示出良好的抗真菌活性[5]。口服剂量为30mg/kg的Terbinafine后，猫、灰狗和红尾鹰的最大血浆水平分别为3.22、4.01和1.2 μg/ml。Terbinafine在猫（8.01 h）、灰狗（8.6 h）和马（8.1 h）中的半衰期差异不显著，而在红尾鹰（17.5 h）和非洲企鹅（17.0 h）中则显著延长[2]。