Field H J, Tewari D, Sutton D, Thackray A M
Centre for Veterinary Science, Cambridge University Veterinary School.
Antimicrob Agents Chemother. 1995 May;39(5):1114-9. doi: 10.1128/AAC.39.5.1114.
A mouse model of herpes simplex virus type 1 infection in an immunocompromised host was established by using cyclosporin-A to impair T-cell function. Following inoculation of herpes simplex virus type 1 into the skin of the ear pinna, cyclosporin-A prolonged virus replication in the skin and neural tissues compared with that in immunocompetent mice. This model was used to investigate the activity of famciclovir (FCV) and valaciclovir (VACV), which are oral products of the antiherpesvirus agents penciclovir and acyclovir, respectively. Both prodrugs gave similar blood profiles of the antiherpesvirus agents in normal and cyclosporin-treated mice. The compounds were administered by the oral route at 50 mg/kg per dose twice daily for 5 days. Both compounds were very effective at clearing infectious virus from the tissues despite the immunosuppression; FCV-treated animals cleared virus from the ear pinna more rapidly than VACV-treated animals. The areas under the concentration-time curve (AUC) for virus replication with time were reduced to 50 and 30% of control values for ear pinna and brain stem, respectively, with VACV therapy and to < 5% in both tissues by FCV. When treatment was continued to day 10, the reductions in AUC for ear and brain stem, respectively, were to 33 and 26% of control values with VACV and to < 3 and < 5% with FCV. However, on cessation of the antiviral treatment, there was a reproducible recurrence of infectious virus in the tissues obtained from VACV-treated mice. The recurrence of infectious virus was also evident after 10 days of treatment with VACV. In mice which had received FCV for 10 or 5 days, these was no resumption of virus replication in the ear pinna or brain stem. When dosing was reduced to once per day, both compounds were less effective at controlling the infection. Nevertheless, no recurrence of infectious virus was observed on cessation of FCV therapy.
通过使用环孢素 A 损害 T 细胞功能，建立了免疫受损宿主单纯疱疹病毒 1 型感染的小鼠模型。将单纯疱疹病毒 1 型接种到耳廓皮肤后，与免疫功能正常的小鼠相比，环孢素 A 延长了病毒在皮肤和神经组织中的复制。该模型用于研究泛昔洛韦（FCV）和伐昔洛韦（VACV）的活性，它们分别是抗疱疹病毒药物喷昔洛韦和阿昔洛韦的口服制剂。在正常小鼠和环孢素处理的小鼠中，这两种前体药物的抗疱疹病毒药物血药浓度曲线相似。化合物通过口服途径给药，剂量为 50 mg/kg，每日两次，共 5 天。尽管存在免疫抑制，但两种化合物在清除组织中的感染性病毒方面都非常有效；FCV 治疗的动物比 VACV 治疗的动物更快地从耳廓清除病毒。VACV 治疗后，耳廓和脑干病毒复制的浓度-时间曲线下面积（AUC）分别降至对照值的 50%和 30%，而 FCV 治疗后两个组织中的 AUC 均降至<5%。当治疗持续到第 10 天时，VACV 治疗后耳廓和脑干的 AUC 分别降至对照值的 33%和 26%，FCV 治疗后分别降至<3%和<5%。然而，停止抗病毒治疗后，从 VACV 治疗的小鼠获得的组织中可重复出现感染性病毒。VACV 治疗 10 天后，感染性病毒的复发也很明显。在接受 FCV 治疗 10 天或 5 天的小鼠中，耳廓或脑干中没有病毒复制的恢复。当给药频率降至每天一次时，两种化合物在控制感染方面效果较差。然而，停止 FCV 治疗后未观察到感染性病毒的复发。
