Castela N, Vermerie N, Chast F, Sauvageon-Martre H, Denis J, Godard V, Goldschmidt P, Pouliquen Y
Service de Pharmacie et de Pharmacologie, Paris, France.
J Ocul Pharmacol. 1994 Summer;10(2):439-51. doi: 10.1089/jop.1994.10.439.
A chronic administration of three ganciclovir gels (0.2%, 0.05%, 0.0125%) was compared with a placebo gel and a 3% acyclovir ophthalmic ointment in the treatment of HSV-1 rabbit keratitis. All the ganciclovir gels showed a clinical efficacy: a significant reduction of the corneal ulcer area, clouding and vascularization (p < 0.05) and a fast inhibition of HSV isolates into tear film with the 0.2% and 0.05% ganciclovir gels. However the efficacy was slower than using acyclovir ointment. No significant difference could be shown between the 0.2% and 0.05% ganciclovir gels or the 0.05% ganciclovir gel and the acyclovir treatment on viral isolation, when it was performed on pooled samples. The distribution of ganciclovir and acyclovir into the rabbit eyes (HPLC methods), were similar but markedly higher in solid tissues than ocular fluids. It might explain the recovery from tissue damages. The mean corneal ganciclovir concentrations were largely higher than ED 50 of ganciclovir for HSV-1. No toxicity was expected, due to very limited systemic availability. This study suggests a comparable activity on HSV-1 superficial keratitis between 0.05%, 0.2% ganciclovir gels and 3% acyclovir ointment. Higher concentration of ganciclovir gels are probably necessary in order to treat the HSV-1 kerato-uveitis.
将三种更昔洛韦凝胶（0.2%、0.05%、0.0125%）长期给药与安慰剂凝胶及3%阿昔洛韦眼膏进行比较，用于治疗单纯疱疹病毒1型（HSV-1）兔角膜炎。所有更昔洛韦凝胶均显示出临床疗效：角膜溃疡面积、混浊及血管化显著减少（p<0.05），且0.2%和0.05%更昔洛韦凝胶能快速抑制泪膜中的HSV分离株。然而，其疗效比使用阿昔洛韦眼膏慢。当对混合样本进行病毒分离时，0.2%和0.05%更昔洛韦凝胶之间或0.05%更昔洛韦凝胶与阿昔洛韦治疗之间在病毒分离方面无显著差异。更昔洛韦和阿昔洛韦在兔眼中的分布（采用高效液相色谱法）相似，但在固体组织中的含量明显高于眼内液。这可能解释了组织损伤的恢复情况。角膜更昔洛韦平均浓度远高于HSV-1的更昔洛韦半数有效剂量（ED 50）。由于全身药物利用率非常有限，预计无毒性。本研究表明，0.05%、0.2%更昔洛韦凝胶与3%阿昔洛韦眼膏对HSV-1浅层角膜炎具有相当的活性。为了治疗HSV-1角膜葡萄膜炎，可能需要更高浓度的更昔洛韦凝胶。
