Nordenfelt E, Widell A, Hansson B G, Löfgren B, Möller-Nielsen C, Oberg B
Acta Pathol Microbiol Immunol Scand B. 1982 Dec;90(6):449-51. doi: 10.1111/j.1699-0463.1982.tb00145.x.
The efficient in vitro inhibition of hepatitis B virus DNA polymerase by trisodium phosphonoformate (PFA, INN: foscarnet sodium) and its low toxicity suggested that PFA could be used as a therapeutic agent for hepatitis B infection. PFA was also found to inhibit woodchuck hepatitis virus (WHV) DNA polymerase in vitro. As a model to test PFA's eventual effect, chronically WHV infected woodchucks were treated with PFA. The animals were treated twice daily in a dosage which gave a minimum serum level of PFA corresponding to an in vitro inhibiting effect on WHV DNA polymerase of about 40%. The concentration in liver tissue was found to be 15% below serum level. The amount of WHV particles in serum was followed by DNA polymerase assay. No effect on WHV production could be seen during 2 weeks' treatment. No change of the in vitro sensitivity to PFA of the WHV DNA polymerase was seen. These results indicate that the WHV associated DNA polymerase has no role in the production of viral particles.
膦甲酸钠三钠（PFA，国际非专利药品名称：膦甲酸钠）对乙肝病毒DNA聚合酶具有高效的体外抑制作用，且毒性较低，这表明PFA可作为治疗乙肝感染的药物。研究还发现PFA在体外可抑制土拨鼠肝炎病毒（WHV）DNA聚合酶。作为测试PFA最终疗效的模型，对慢性感染WHV的土拨鼠用PFA进行治疗。动物每天接受两次治疗，所用剂量使血清中PFA的最低水平对应于对WHV DNA聚合酶约40%的体外抑制作用。结果发现肝组织中的浓度比血清水平低15%。通过DNA聚合酶测定来跟踪血清中WHV颗粒的数量。在为期2周的治疗期间，未观察到对WHV产生有任何影响。未发现WHV DNA聚合酶对PFA的体外敏感性发生变化。这些结果表明，与WHV相关的DNA聚合酶在病毒颗粒的产生过程中不起作用。
