泛昔洛韦和阿昔洛韦体内外抗疱疹病毒活性的比较研究  

Comparison of efficacies of famciclovir with acyclovir against herpes simple virus type 1 and 2 in vitro and in vivo

作　　者：李建农[1] 滕立[1] 陈鸿珊[1] 蒋宁[2] 蒋建东[1] 

机构地区：[1]中国医学科学院中国协和医科大学医药生物技术研究所,北京100050 [2]四川抗菌素工业研究所,四川成都610051

出　　处：《中国药学杂志》2003年第6期423-426,共4页Chinese Pharmaceutical Journal

摘　　要：目的　观察泛昔洛韦和阿昔洛韦在体内外实验模型中的抗疱疹病毒药效。方法　用CPE ,MTT染色法和空斑法观察两药在Vero细胞培养内对疱疹病毒 1型 (HSV 1 )和 2型 (HSV 2 )病毒的抑制作用 ;在疱疹病毒 1型小鼠急性脑炎和豚鼠皮肤感染模型以及疱疹病毒 2型小鼠阴道炎模型上观察两药体内对HSV 1和HSV 2感染的治疗效果。结果　在细胞培养内 ,泛昔洛韦对HSV 1和HSV 2无明显抑制活性 (IC50 >1 0 0 0 μg·mL- 1 ) ,阿昔洛韦对HSV有显著的抑制作用。动物口服泛昔洛韦和阿昔洛韦能显著降低HSV 1腹腔感染小鼠引起的死亡和延长小鼠生命 ,泛昔洛韦和阿昔洛韦保护小鼠死亡的ED50 分别为2 9 .9mg·kg- 1 和 >1 0 0mg·kg- 1 ,延长小鼠生命的ED50 分别为 43 .6mg·kg- 1 和 >1 0 0mg·kg- 1 ;对HSV 1感染豚鼠皮肤疱疹的抑制率 ,口服泛昔洛韦为 75 .0 %～ 77.8% ,阿昔洛韦为 45 .0 %～ 41 .7% ,泛昔洛韦优于阿昔洛韦 ;对HSV 2阴道感染小鼠死亡率和延长小鼠生命 ,口服泛昔洛韦和阿昔洛韦的ED50 分别是 53 .4 ,53 .4和 44 .6 ,39.5mg·kg- 1 。结论　①在细胞培养内 ,泛昔洛韦无抗疱疹病毒作用 ,阿昔洛韦有很强的抗疱疹病毒活性。②对于HSV 1引起的脑炎和皮肤感染 ,口服泛昔洛韦优于阿昔洛韦 ;对于HSV 2引起的阴道炎 。OBJECTIVE: To compare the anti-herpetic activities of famciclovir with acyclovir in vitro and in vivo. METHODS: The anti-herpetic activities in cell cultures were tested by CPE, MTT staining and plaque reduction assays respectively. Animal models of acute herpes encephalitis and vaginitis in mice, as well as guinea pigs cutaneous infection were used to evaluate the anti-herpetic effect in vivo. RESULTS: In vitro experiments showed that famciclovir 1 000 μg&middotmL-1 had no inhibition on both HSV-1 and HSV-2 in cell cultures, whereas acyclovir showed significant inhibition in the 3 assays mentioned above with IC50-1 on HSV-1 and IC50 of 15.95, 13.69 and 6.27 μg&middotmL-1 on HSV-2 respectively. The in vivo experiments showed different results from that of cell culture. Famciclovir and acyclovir given orally significantly reduced mortality and prolonged the survival of mice with HSV-1 encephalitis. ED50 of famciclovir and acyclovir were 29.9 mg&middotkg-1 and > 100 mg&middotkg-1 respectively for the mortality, and 43.6 mg&middot kg-1 and > 100 mg&middotkg-1 for increasing survival time respectively. In the HSV-1 guinea pigs cutaneous infection, oral administration of famciclovir reduced the cumulative lesion soores by 75.0% ∼ 77.8%, higher than that by acyclovir (45.0% ∼ 41.7%). Oral treatment with famciclovir and acyclovir also remarkably reduced mortality and prolonged the survival time of the mice with HSV-2 genital infection. The ED50 for the mortality and survival time were 53.4 and 44.6 mg&middotkg-1 for famciclovir and 53.4 and 39.5 mg&middotkg-1 for acyclovir, respectively. CONCLUSION: These data indicated that famciclovir had no anti-herpetic activity in cell cultures, while acyclovir showed significant inhibition on herpes virus and is recommended for topical use. For the HSV-1 in vivo models, the efficacy of famciclovir was significantly better than that of acyclovir. The two compounds showed similar activity to HSV-2 in vivo.

关 键 词：泛昔洛韦 阿昔洛韦 抗疱疹病毒活性 比较研究 

分 类 号：R978.7[医药卫生—药品]