Machida H, Ikeda T, Ashida N
Biology Laboratory, Yamasa Shoyu Co. Ltd., Choshi, Japan.
Antiviral Res. 1990 Aug;14(2):99-107. doi: 10.1016/0166-3542(90)90047-b.
1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) and acyclovir were compared for their antiviral effects against herpes simplex virus type 1 (HSV-1) model infections in mice. Both drugs were not toxic to mice when they were administered orally by the same schedule used for therapeutic experiments. Brovavir was less toxic than acyclovir when injected by the intraperitoneal (i.p.) route. Marked efficacies of brovavir by either oral or i.p. administration were demonstrated in both experimental encephalitis and i.p. infection with HSV-1 WT-51 strain. Treatment with brovavir at a dose of 15 or 25 mg/kg twice daily resulted in increasing both survival rate and mean survival time of the infected mice. On the contrary, acyclovir showed only marginal effect against the experimental encephalitis. Survival rates of mice treated with brovavir were higher than those treated with acyclovir at corresponding doses with statistical significance. The superiority of brovavir was also found in the intracerebral infection with strain VR-3, a highly virulent strain for mice. Brovavir, but not acyclovir, at a dose of 200 mg/kg reduced the mortality. Acyclovir, however, were significantly effective in reducing mortality of systemically infected mice by both oral and i.p. administrations. The effective dose of acyclovir was lower than that of brovavir against i.p. infection with strain WT-51. Differences in mortality of strain VR-3-infected mice were statistically significant between acyclovir- and brovavir-treated groups.
比较了1-β-D-阿拉伯呋喃糖基-E-5-(2-溴乙烯基)尿嘧啶(溴夫定)和阿昔洛韦对小鼠单纯疱疹病毒1型(HSV-1)模型感染的抗病毒作用。按照用于治疗实验的相同给药方案口服时,两种药物对小鼠均无毒。经腹腔(i.p.)途径注射时,溴夫定的毒性低于阿昔洛韦。在实验性脑炎和HSV-1 WT-51株的腹腔感染中,均证明了溴夫定经口服或腹腔注射给药均具有显著疗效。以15或25mg/kg的剂量每日两次用溴夫定治疗,可提高感染小鼠的存活率和平均存活时间。相反,阿昔洛韦对实验性脑炎仅显示出微弱的作用。用溴夫定治疗的小鼠的存活率高于用相应剂量阿昔洛韦治疗的小鼠,具有统计学意义。在对小鼠具有高毒力的VR-3株的脑内感染中也发现了溴夫定的优势。以200mg/kg的剂量使用溴夫定可降低死亡率,而阿昔洛韦则不能。然而,阿昔洛韦通过口服和腹腔注射给药对全身感染小鼠的死亡率均有显著降低作用。在对WT-51株的腹腔感染中,阿昔洛韦的有效剂量低于溴夫定。阿昔洛韦和溴夫定治疗组之间,VR-3株感染小鼠的死亡率差异具有统计学意义。