Maggs David J, Clarke Heather E
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Am J Vet Res. 2004 Apr;65(4):399-403. doi: 10.2460/ajvr.2004.65.399.
To establish the in vitro efficacy of 4 novel drugs (ie, ganciclovir, cidofovir, penciclovir, and foscarnet) against feline herpesvirus type-1 (FHV-1) and compare their antiviral efficacy with that of acyclovir and idoxuridine.
Cultured Crandell-Reese feline kidney (CRFK) cells and FHV-1 strain 727
For each drug, antiviral effect was estimated by use of conventional plaque-reduction assays, and inhibitory concentration 50 (IC50; drug concentration at which plaque numbers were reduced by 50% relative to the number of plaques for nontreated control wells) was calculated. To determine whether observed antiviral effects were related to alterations in the number or viability of CRFK cells, cytotoxicity assays were performed at 1, 2, and 10 times the median IC50 for each antiviral drug.
Median IC50 for each drug was as follows: ganciclovir, 5.2 microM; cidofovir, 11.0 microM; penciclovir, 13.9 microM; foscarnet, 232.9 microM; idoxuridine, 4.3 microM; and acyclovir, 57.9 microM. Obvious changes in morphologic characteristics, confluence, or viability of CRFK cells were not observed at concentrations up to and including 2 times the IC50 for each drug.
In vitro efficacy of idoxuridine and ganciclovir against FHV-1 was approximately equivalent and about twice that of cidofovir and penciclovir. Foscarnet appeared to be comparatively ineffective. Given the reasonable clinical efficacy of idoxuridine in cats infected with FHV-1, clinical trials of ganciclovir, cidofovir, and penciclovir or their prodrug forms appear to be warranted.
确定4种新药(即更昔洛韦、西多福韦、喷昔洛韦和膦甲酸钠)对猫疱疹病毒1型(FHV-1)的体外疗效,并将它们的抗病毒疗效与阿昔洛韦和碘苷进行比较。
培养的克兰德尔-里斯猫肾(CRFK)细胞和FHV-1毒株727
对于每种药物,通过传统的蚀斑减少试验评估抗病毒效果,并计算半数抑制浓度(IC50;相对于未处理对照孔的蚀斑数,蚀斑数减少50%时的药物浓度)。为了确定观察到的抗病毒效果是否与CRFK细胞数量或活力的改变有关,在每种抗病毒药物的半数抑制浓度的1倍、2倍和10倍浓度下进行细胞毒性试验。
每种药物的半数抑制浓度中位数如下:更昔洛韦,5.2微摩尔;西多福韦,11.0微摩尔;喷昔洛韦,13.9微摩尔;膦甲酸钠,232.9微摩尔;碘苷,4.3微摩尔;阿昔洛韦,57.9微摩尔。在每种药物浓度达到并包括半数抑制浓度的2倍时,未观察到CRFK细胞形态特征、汇合度或活力的明显变化。
碘苷和更昔洛韦对FHV-1的体外疗效大致相当,约为西多福韦和喷昔洛韦的两倍。膦甲酸钠似乎相对无效。鉴于碘苷在感染FHV-1的猫中具有合理的临床疗效,更昔洛韦、西多福韦和喷昔洛韦或其前药形式的临床试验似乎是有必要的。