Mihich E, Grindey G B
Cancer. 1977 Jul;40(1 Suppl):534-43. doi: 10.1002/1097-0142(197707)40:1+<534::aid-cncr2820400720>3.0.co;2-3.
In combination chemotherapy, the type of drug interactions can be divided into three broad categories: 1) combinations based on cooperative effects of active drugs; 2) combinations in which the effectiveness of an active drug is increased by the concurrent administration of an inactive agent; and 3) combination of an active drug with an agent capable of selectively reversing the toxicity of the first drug. Many concepts have been proposed to explain the synergistic interaction between two active drugs at the level of the target cell. These include multiple inhibition of a single enzyme, enhanced activation, decreased inactivation, increased drug uptake, sequential blockade, concurrent inhibition, complimentary inhibition, and concerted inhibition. The therapeutic advantage of combination chemotherapy may reside in the whole organism, reflecting increased bioavailability of drug, reduced dose-limiting toxicity or reduced impairment of host defenses; it may reside in the tumor cells, reflecting the multiple molecular mechanisms of interaction mentioned above. Examples discussed include among others methotrexate plus citrovorum factor, thymidine or allopurinol, araC plus tetrahydrouridine and 3-deazauridine plus testosterone.
在联合化疗中，药物相互作用的类型可大致分为三大类：1）基于活性药物协同作用的联合用药；2）通过同时给予非活性药物来提高活性药物疗效的联合用药；3）活性药物与能够选择性逆转第一种药物毒性的药物联合使用。人们提出了许多概念来解释两种活性药物在靶细胞水平上的协同相互作用。这些概念包括对单一酶的多重抑制、增强激活、减少失活、增加药物摄取、顺序阻断、同时抑制、互补抑制和协同抑制。联合化疗的治疗优势可能存在于整个机体中，表现为药物生物利用度提高、剂量限制性毒性降低或宿主防御功能受损减轻；也可能存在于肿瘤细胞中，体现为上述多种分子相互作用机制。所讨论的例子包括甲氨蝶呤加亚叶酸、胸腺嘧啶核苷或别嘌呤醇，阿糖胞苷加四氢尿苷，以及3-去氮尿苷加睾酮等。
