Gordon Y J, Romanowski E G, Araullo-Cruz T
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pennsylvania.
Cornea. 1994 Nov;13(6):516-20.
Previously, we demonstrated that HPMPC, a new, broad-spectrum antiviral agent, inhibited adenovirus type 5 in the New Zealand (NZ) rabbit ocular model (Cornea 1992; 11:529-33). Historically, no antiviral agent has been demonstrated to be effective against both herpes simplex virus type 1 (HSV-1) and adenovirus eye infections in an experimental animal model. In this study, we compared topical 0.2% HPMPC to 1% trifluridine and vehicle control in the NZ rabbit HSV-1 keratitis model. Using a double-masked, two-eye design, NZ rabbits were inoculated in both eyes with HSV-1 W strain (10(5) pfu/eye), and dendritic keratitis and HSV-1 ocular titers were measured serially. Compared with the control group, both topical 0.2% HPMPC and 1% trifluridine significantly reduced healing time of HSV-1 dendritic keratitis, lowered HSV-1 ocular titers on days 3 through 11, and shortened duration of HSV-1 shedding in the tear film. For all outcome parameters measured, topical 0.2% HPMPC was as effective as 1% trifluridine. A new concept of a broad-spectrum topical antiviral agent was shown to be effective against HSV-1 in an NZ rabbit keratitis model, and further development toward clinical application appears desirable.
此前，我们证实新型广谱抗病毒药物HPMPC在新西兰兔眼模型中可抑制5型腺病毒（《角膜》，1992年；11:529 - 33）。从历史上看，在实验动物模型中，尚无抗病毒药物被证明对单纯疱疹病毒1型（HSV - 1）和腺病毒眼部感染均有效。在本研究中，我们在新西兰兔HSV - 1角膜炎模型中，将0.2%的HPMPC局部用药与1%的三氟尿苷及赋形剂对照进行比较。采用双盲、双眼设计，给新西兰兔双眼接种HSV - 1 W株（10⁵ 蚀斑形成单位/眼），并连续测量树枝状角膜炎及HSV - 1眼内滴度。与对照组相比，局部应用0.2%的HPMPC和1%的三氟尿苷均显著缩短了HSV - 1树枝状角膜炎的愈合时间，降低了第3至11天的HSV - 1眼内滴度，并缩短了泪膜中HSV - 1脱落的持续时间。对于所测量的所有结果参数，局部应用0.2%的HPMPC与1%的三氟尿苷效果相当。一种新型广谱局部抗病毒药物的概念在新西兰兔角膜炎模型中被证明对HSV - 1有效，进一步向临床应用发展似乎是可取的。
