Trousdale M D, Law J L, Yarber F A, Watanabe K A, Fox J J
Doheny Eye Institute, Los Angeles, CA 90033.
Antiviral Res. 1992 Feb;17(2):157-67. doi: 10.1016/0166-3542(92)90049-b.
The nucleoside analog 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5- ethyluracil (FEAU) was tested in a rabbit model of acute herpetic keratitis and its effectiveness compared with that of acyclovir (ACV). FEAU or ACV was applied topically 3 times daily, beginning 3 days post-HSV-1 inoculation and continued for a period of 7 days. FEAU at a concentration of 1% (w/v) or 3% ACV resulted in significant lessening of the severity of corneal lesions, conjunctivitis, iritis, and corneal clouding at 24 to 48 h after beginning chemotherapy. No toxic reaction was observed in any rabbit eyes treated with either FEAU or ACV. The duration of virus shedding into tear film and colonization of the trigeminal ganglia, however, were not reduced by either FEAU or ACV treatment begun 3 days post-inoculation. Fifty percent effective dose (ED50) of FEAU determinations performed on isolates from tear film and on the virus inoculum in secondary rabbit kidney cultures yielded a range of 4.6-7 microM, with two in vitro resistant isolates having ED50S of greater than or equal to 1500 microM of FEAU. Fifty percent cell growth inhibition for FEAU was 3000 microM at 72 h.
核苷类似物1-(2'-脱氧-2'-氟-β-D-阿拉伯呋喃糖基)-5-乙基尿嘧啶(FEAU)在兔急性疱疹性角膜炎模型中进行了测试，并将其有效性与阿昔洛韦(ACV)进行了比较。FEAU或ACV在单纯疱疹病毒1型接种后3天开始每天局部应用3次，并持续7天。浓度为1%(w/v)的FEAU或3%的ACV在开始化疗后24至48小时显著减轻了角膜病变、结膜炎、虹膜炎和角膜混浊的严重程度。在用FEAU或ACV治疗的任何兔眼中均未观察到毒性反应。然而，接种后3天开始的FEAU或ACV治疗均未减少病毒向泪膜的脱落持续时间和三叉神经节的定植。对泪膜分离株和二代兔肾培养物中的病毒接种物进行FEAU的半数有效剂量(ED50)测定，结果为4.6-7 microM，有两个体外耐药分离株的FEAU ED50大于或等于1500 microM。FEAU在72小时时对细胞生长的半数抑制浓度为3000 microM。
