西多福韦、曲氟尿苷和阿昔洛韦在单纯疱疹病毒1型兔角膜炎模型中的抗病毒疗效比较。

Comparative antiviral efficacies of cidofovir, trifluridine, and acyclovir in the HSV-1 rabbit keratitis model.

作者信息

Romanowski E G, Bartels S P, Gordon Y J

机构信息

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pennsylvania, USA.

出版信息

Invest Ophthalmol Vis Sci. 1999 Feb;40(2):378-84.

PMID:9950596

Abstract

PURPOSE

To determine the relative antiviral inhibitory activity of topical 1% and 0.5% cidofovir, topical trifluridine (Viroptic; Burroughs-Wellcome, Research Triangle Park, NC), and topical acyclovir (Zovirax; The Wellcome Foundation, London, UK) during a 7-day period for the treatment of herpes simplex virus type 1 (HSV-1) keratitis and HSV-1 replication in the New Zealand rabbit ocular model.

METHODS

In a series of four experiments using a two-eye design, a total of 80 New Zealand rabbits were inoculated in both eyes with HSV-1 McKrae after epithelial scarification. Forty-eight hours after inoculation, the rabbits were randomly assigned to a treatment group. Five treatment groups (16 rabbits/group) were evaluated: I, 1% cidofovir, twice daily for 7 days; II, 0.5% cidofovir, twice daily for 7 days; III, 3% acyclovir ointment, five times daily for 7 days; IV, 1% trifluridine, nine times daily for 3 days, then 4 times daily for 4 days; and V, control vehicle twice daily for 7 days. HSV-1 dendritic keratitis was graded in a masked fashion by slit-lamp examination on days 2, 3, 5, 7, 9, 11, and 14. Ocular viral cultures were obtained after slit-lamp examination on days 1, 3, 5, 7, 9, 11, and 14.

RESULTS

Compared with the control group, all four treatment groups demonstrated significantly lower viral titers, fewer HSV-1-positive eyes/total during the treatment period, lower keratitis scores, fewer eyes with keratitis/total, and a shorter time to resolution of keratitis. Within the treatment groups, the 1% and 0.5% cidofovir treatments were significantly more effective than acyclovir and trifluridine as measured by the previous viral and keratitis parameters.

CONCLUSIONS

Topical 1% and 0.5% cidofovir both appeared to be significantly more efficacious than topical trifluridine and acyclovir, during a 7-day course, in the treatment of experimental HSV-1 ocular disease in the New Zealand rabbit keratitis model.

摘要

目的

在新西兰兔眼模型中，确定局部用1%和0.5%西多福韦、局部用三氟尿苷（Viroptic；百时美施贵宝公司，北卡罗来纳州三角研究园）和局部用阿昔洛韦（Zovirax；英国伦敦威康信托基金会）在7天治疗期内对单纯疱疹病毒1型（HSV-1）角膜炎的相对抗病毒抑制活性以及HSV-1复制情况。

方法

在一系列采用双眼设计的四项实验中，共80只新西兰兔在角膜上皮划痕后双眼接种HSV-1 McKrae株。接种后48小时，将兔子随机分配至治疗组。评估五个治疗组（每组16只兔子）：I组，1%西多福韦，每日两次，共7天；II组，0.5%西多福韦，每日两次，共7天；III组，3%阿昔洛韦眼膏，每日五次，共7天；IV组，1%三氟尿苷，前3天每日九次，后4天每日四次；V组，对照赋形剂，每日两次，共7天。在第2、3、5、7、9、11和14天通过裂隙灯检查以盲法对HSV-1树枝状角膜炎进行分级。在第1、3、5　、7、9、11和14天裂隙灯检查后获取眼病毒培养物。