Crane L R, Milne D A, Sunstrum J C, Lerner A M
Antimicrob Agents Chemother. 1984 Oct;26(4):557-62. doi: 10.1128/AAC.26.4.557.
The effects of double and triple combinations of acyclovir (ACV), adenine arabinoside (ara-A), arabinosyl hypoxanthine, or interferon on herpes simplex virus type 2 in mouse embryo fibroblasts were measured. These in vitro data were compared with results obtained in mice infected intravaginally with herpes simplex virus type 2 and treated intraperitoneally with low- and high-dose combinations of ACV, ara-A, or polyriboinosinic-polyribocytidylic acid(poly-L-lysine)carboxymethylcellulose complex [poly IC(LC)], an interferon inducer. Although all double combinations and one triple combination evoked synergistic reactions in vitro, results did not necessarily predict in vivo observations. In vivo synergy was observed when combinations of ACV and ara-A and low doses of ara-A-ACV-poly IC(LC) were used. However, toxicity was seen with full-dose nucleoside-poly IC(LC) doublets. The full-dose ACV-ara-A combination completely prevented progression beyond vaginitis, with all animals surviving. The ara-A-ACV results observed in mice, together with in vivo data of others, suggest that this combination might prove clinically useful for certain herpes simplex virus type 2 infections.
测定了阿昔洛韦(ACV)、阿糖腺苷(ara-A)、阿糖次黄嘌呤或干扰素的双重及三重组合对小鼠胚胎成纤维细胞中2型单纯疱疹病毒的作用。将这些体外实验数据与经阴道感染2型单纯疱疹病毒并经腹腔注射低剂量和高剂量ACV、ara-A或聚肌苷酸-聚胞苷酸(聚-L-赖氨酸)羧甲基纤维素复合物[聚肌胞(LC),一种干扰素诱导剂]治疗的小鼠所获得的结果进行了比较。尽管所有双重组合和一种三重组合在体外均引发了协同反应,但结果并不一定能预测体内观察结果。当使用ACV与ara-A的组合以及低剂量的ara-A-ACV-聚肌胞(LC)时,在体内观察到了协同作用。然而,全剂量核苷-聚肌胞(LC)双重组合出现了毒性。全剂量ACV-ara-A组合完全阻止了病情发展至阴道炎之外,所有动物均存活。在小鼠中观察到的ara-A-ACV结果,连同其他研究的体内数据表明,这种组合可能在临床上对某些2型单纯疱疹病毒感染有用。